Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Review Article

Leucine Rich Repeat Proteins: Sequences, Mutations, Structures and Diseases

Author(s): Norio Matsushima*, Shintaro Takatsuka, Hiroki Miyashita and Robert H. Kretsinger

Volume 26, Issue 2, 2019

Page: [108 - 131] Pages: 24

DOI: 10.2174/0929866526666181208170027

Abstract

Mutations in the genes encoding Leucine Rich Repeat (LRR) containing proteins are associated with over sixty human diseases; these include high myopia, mitochondrial encephalomyopathy, and Crohn’s disease. These mutations occur frequently within the LRR domains and within the regions that shield the hydrophobic core of the LRR domain. The amino acid sequences of fifty-five LRR proteins have been published. They include Nod-Like Receptors (NLRs) such as NLRP1, NLRP3, NLRP14, and Nod-2, Small Leucine Rich Repeat Proteoglycans (SLRPs) such as keratocan, lumican, fibromodulin, PRELP, biglycan, and nyctalopin, and F-box/LRR-repeat proteins such as FBXL2, FBXL4, and FBXL12. For example, 363 missense mutations have been identified. Replacement of arginine, proline, or cysteine by another amino acid, or the reverse, is frequently observed. The diverse effects of the mutations are discussed based on the known structures of LRR proteins. These mutations influence protein folding, aggregation, oligomerization, stability, protein-ligand interactions, disulfide bond formation, and glycosylation. Most of the mutations cause loss of function and a few, gain of function.

Keywords: Leucine rich repeat protein, mutations, diseases, amino acid preference, aggregation, misfolding, protein-ligand interactions.

Next »
Graphical Abstract
[1]
Kobe, B.; Deisenhofer, J. The leucine-rich repeat: A versatile binding motif. Trends Biochem. Sci., 1994, 19, 415-421.
[2]
Matsushima, N.; Kretysinger, R. Leicine rich repeats: Sequences, structures, ligand - interactions, and evolution; LAMBERT Academic Publishing: Saarbrücken, 2016, pp. 1-134.
[3]
Miyashita, H.; Kuroki, Y.; Matsushima, N. Novel leucine rich repeat domains in proteins from unicellular eukaryotes and bacteria. Protein Pept. Lett., 2014, 21, 2-305.
[4]
Kobe, B.; Kajava, A.V. The leucine-rich repeat as a protein recognition motif. Curr. Opin. Struct. Biol., 2001, 11, 725-732.
[5]
Matsushima, N.; Miyashita, H.; Mikami, T.; Kuroki, Y. A nested leucine rich repeat (LRR) domain: The precursor of LRRs is a ten or eleven residue motif. BMC Microbiol., 2010, 10, 235.
[6]
Enkhbayar, P.; Miyashita, H.; Kretsinger, R.; Matsushima, N. Helical parameters and correlations of tandem leucine rich repeats in proteins. J. Proteomics Bioinform., 2014, 7, 139-150.
[7]
Bella, J.; Hindle, K.L.; McEwan, P.A.; Lovell, S.C. The leucine-rich repeat structure. Cell. Mol. Life Sci., 2008, 65, 2307-2333.
[8]
Ng, A.C.; Eisenberg, J.M.; Heath, R.J.; Huett, A.; Robinson, C.M.; Nau, G.J.; Xavier, R.J. Human leucine-rich repeat proteins: A genome-wide bioinformatic categorization and functional analysis in innate immunity. Proc. Natl. Acad. Sci. USA, 2011, 108(Suppl. 1), 4631-4638.
[9]
Matsushima, N.; Tachi, N.; Kuroki, Y.; Enkhbayar, P.; Osaki, M.; Kamiya, M.; Kretsinger, R.H. Structural analysis of leucine-rich-repeat variants in proteins associated with human diseases. Cell. Mol. Life Sci., 2005, 62, 2771-2791.
[10]
Desai, S.S.; Roy, B.S.; Mahale, S.D. Mutations and polymorphisms in FSH receptor: Functional implications in human reproduction. Reproduction, 2013, 146, R235-R248.
[11]
Kleinau, G.; Worth, C.L.; Kreuchwig, A.; Biebermann, H.; Marcinkowski, P.; Scheerer, P.; Krause, G. Structural-functional features of the thyrotropin receptor: A class A G-protein-coupled receptor at work. Front. Endocrinol. (Lausanne), 2017, 8, 86.
[12]
Li, R.; Emsley, J. The organizing principle of the platelet glycoprotein Ib-IX-V complex. J. Thromb. Haemost., 2013, 11, 605-614.
[13]
Domene, H.M.; Hwa, V.; Jasper, H.G.; Rosenfeld, R.G. Acid-labile subunit (ALS) deficiency. Best Pract. Res. Clin. Endocrinol. Metab., 2011, 25, 101-113.
[14]
Fritz, J.H.; Ferrero, R.L.; Philpott, D.J.; Girardin, S.E. Nod-like proteins in immunity, inflammation and disease. Nat. Immunol., 2006, 7, 1250-1257.
[15]
Steimle, V.; Otten, L.A.; Zufferey, M.; Mach, B. Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome). Cell, 1993, 75, 135-146.
[16]
Bontron, S.; Steimle, V.; Ucla, C.; Eibl, M.M.; Mach, B. Two novel mutations in the MHC class II transactivator CIITA in a second patient from MHC class II deficiency complementation group A. Hum. Genet., 1997, 99, 541-546.
[17]
Dziembowska, M.; Fondaneche, M.C.; Vedrenne, J.; Barbieri, G.; Wiszniewski, W.; Picard, C.; Cant, A.J.; Steimle, V.; Charron, D.; Alca-Loridan, C.; Fischer, A.; Lisowska-Grospierre, B. Three novel mutations of the CIITA gene in MHC class II-deficient patients with a severe immunodeficiency. Immunogenetics, 2002, 53, 821-829.
[18]
Peijnenburg, A.; Van den Berg, R.; Van Eggermond, M.J.; Sanal, O.; Vossen, J.M.; Lennon, A.M.; Alcaide-Loridan, C.; Van den Elsen, P.J. Defective MHC class II expression in an MHC class II deficiency patient is caused by a novel deletion of a splice donor site in the MHC class II transactivator gene. Immunogenetics, 2000, 51, 42-49.
[19]
Grandemange, S.; Sanchez, E.; Louis-Plence, P.; Tran Mau-Them, F.; Bessis, D.; Coubes, C.; Frouin, E.; Seyger, M.; Girard, M.; Puechberty, J.; Costes, V.; Rodière, M.; Carbasse, A.; Jeziorski, E.; Portales, P.; Sarrabay, G.; Mondain, M.; Jorgensen, C.; Apparailly, F.; Hoppenreijs, E.; Touitou, I.; Geneviève, D. A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis). Ann. Rheum. Dis., 2017, 76, 191-1198.
[20]
Levandowski, C.B.; Mailloux, C.M.; Ferrara, T.M.; Gowan, K.; Ben, S.; Jin, Y.; McFann, K.K.; Holland, P.J.; Fain, P.R.; Dinarello, C.A.; Spritz, R.A. NLRP1 haplotypes associated with vitiligo and autoimmunity increase interleukin-1beta processing via the NLRP1 inflammasome. Proc. Natl. Acad. Sci. USA, 2013, 110, 2952-2956.
[21]
Zhong, F.L.; Mamai, O.; Sborgi, L.; Boussofara, L.; Hopkins, R.; Robinson, K.; Szeverenyi, I.; Takeichi, T.; Balaji, R.; Lau, A.; Tye, H.; Roy, K.; Bonnard, C.; Ahl, P.J.; Jones, L.A.; Baker, P.J.; Lacina, L.; Otsuka, A.; Fournie, P.R.; Malecaze, F.; Lane, E.B.; Akiyama, M.; Kabashima, K.; Connolly, J.E.; Masters, S.L.; Soler, V.J.; Omar, S.S.; McGrath, J.A.; Nedelcu, R.; Gribaa, M.; Denguezli, M.; Saad, A.; Hiller, S.; Reversade, B. Germline NLRP1 mutations cause skin inflammatory and cancer susceptibility syndromes via inflammasome activation. Cell, 2016, 167, 187-202.
[22]
Frenkel, J.; van Kempen, M.J.; Kuis, W.; van Amstel, H.K. Variant chronic infantile neurologic, cutaneous, articular syndrome due to a mutation within the leucine-rich repeat domain of CIAS1. Arthritis Rheum., 2004, 50, 2719-2720.
[23]
Kubota, K.; Ohnishi, H.; Teramoto, T.; Matsui, E.; Murase, K.; Kanoh, H.; Kato, Z.; Kaneko, H.; Seishima, M.; Kondo, N. In vitro analysis of the functional effects of an NLRP3 G809S variant with the co-existence of MEFV haplotype variants in atypical autoinflammatory syndrome. J. Clin. Immunol., 2013, 33, 325-334.
[24]
Wang, C.M.; Dixon, P.H.; Decordova, S.; Hodges, M.D.; Sebire, N.J.; Ozalp, S.; Fallahian, M.; Sensi, A.; Ashrafi, F.; Repiska, V.; Zhao, J.; Xiang, Y.; Savage, P.M.; Seckl, M.J.; Fisher, R.A. Identification of 13 novel NLRP7 mutations in 20 families with recurrent hydatidiform mole; missense mutations cluster in the leucine-rich region. J. Med. Genet., 2009, 46, 569-575.
[25]
Murdoch, S.; Djuric, U.; Mazhar, B.; Seoud, M.; Khan, R.; Kuick, R.; Bagga, R.; Kircheisen, R.; Ao, A.; Ratti, B.; Hanash, S.; Rouleau, G.A.; Slim, R. Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans. Nat. Genet., 2006, 38, 300-302.
[26]
Nguyen, N.M.; Slim, R. Genetics and epigenetics of recurrent hydatidiform moles: Basic science and genetic counselling. Curr. Obstet. Gynecol. Rep., 2014, 3, 55-64.
[27]
Westerveld, G.H.; Korver, C.M.; van Pelt, A.M.; Leschot, N.J.; van der Veen, F.; Repping, S.; Lombardi, M.P. Mutations in the testis-specific NALP14 gene in men suffering from spermatogenic failure. Hum. Reprod., 2006, 21, 3178-3184.
[28]
Sjoblom, T.; Jones, S.; Wood, L.D.; Parsons, D.W.; Lin, J.; Barber, T.D.; Mandelker, D.; Leary, R.J.; Ptak, J.; Silliman, N. Szabo, S.; Buckhaults, P.; Farrell, C.; Meeh, P.; Markowitz, S.D.; Willis, J.; Dawson, D.; Willson, J.K.; Gazdar, A.F.; Hartigan, J.; Wu, L.; Liu, C.; Parmigiani, G.; Park, B.H.; Bachman, K.E.; Papadopoulos, N.; Vogelstein, B.; Kinzler, K.W.; Velculescu, V.E. The consensus coding sequences of human breast and colorectal cancers. Science, 2006, 314, 268-274.
[29]
Ogura, Y.; Bonen, D.K.; Inohara, N.; Nicolae, D.L.; Chen, F.F.; Ramos, R.; Britton, H.; Moran, T.; Karaliuskas, R.; Duerr, R.H.; Achkar, J.P.; Brant, S.R.; Bayless, T.M.; Kirschner, B.S.; Hanauer, S.B.; Nuñez, G.; Cho, J.H. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature, 2001, 411, 603-606.
[30]
Hugot, J.P.; Chamaillard, M.; Zouali, H.; Lesage, S.; Cezard, J.P.; Belaiche, J.; Almer, S.; Tysk, C.; O’Morain, C.A.; Gassull, M.; Binder, V.; Finkel, Y.; Cortot, A.; Modigliani, R.; Laurent-Puig, P.; Gower-Rousseau, C.; Macry, J.; Colombel, J.F.; Sahbatou, M.; Thomas, G. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature, 2001, 411, 599-603.
[31]
Hampe, J. Cuthbert. A.; Croucher. P.J.; Mirza. M.M.; Mascheretti, S.; Fisher, S.; Frenzel, H.; King, K.; Hasselmeyer, A.; MacPherson, A.J.; Bridger, S.; van Deventer, S.; Forbes, A.; Nikolaus, S.; Lennard-Jones, J.E.; Foelsch, U.R.; Krawczak, M.; Lewis, C.; Schreiber, S.; Mathew, C.G. Association between insertion mutation in NOD2 gene and Crohn’s disease in German and British populations. Lancet, 2001, 357, 1925-1928.
[32]
Lakatos, P.L.; Lakatos, L.; Szalay, F.; Willheim-Polli, C.; Osterreicher, C.; Tulassay, Z.; Molnar, T.; Reinisch, W. Papp, J/; Mozsik, G.; Ferenci. P.; Hungarian IBD Study Group. Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn’s disease: phenotype-genotype correlations. World J. Gastroenterol., 2005, 11, 1489-1495.
[33]
Girardelli, M.; Vuch, J.; Tommasini, A.; Crovella, S.; Bianco, A.M. Novel missense mutation in the NOD2 gene in a patient with early onset ulcerative colitis: Causal or chance association? Int. J. Mol. Sci., 2014, 15, 3834-3841.
[34]
Moghaddas, F.; Zeng, P.; Zhang, Y.; Schützle, H.; Brenner, S.; Hofmann, S.R.; Berner, R.; Zhao, Y.; Lu, B.; Chen, X.; Zhang, L.; Cheng, S.; Winkler, S.; Lehmberg, K.; Canna, S.W.; Czabotar, P.E.; Wicks, I.P.; De Nardo, D.; Hedrich, C.M.; Zeng, H.; Masters, S.L. Autoinflammatory mutation in NLRC4 reveals a leucine-rich repeat (LRR)-LRR oligomerization interface J. Allergy. Clin. Immunol, 2018. S0091-6749(18)30710-3.
[35]
Motta, V.; Soares, F.; Sun, T.; Philpott, D.J. NOD-like receptors: Versatile cytosolic sentinels. Physiol. Rev., 2015, 95, 149-178.
[36]
Almannai, M.; Dai, H.; El-Hattab, A.; Wong, L. Gene Reviews: FBXL4-Related Encephalomyopathic Mitochondrial DNA Depletion Syndrome. 2017.Gene Reviews; Adam, M.P.; Ardinger, H.H.; Pagon, R.A.; Wallace, S.E.; Bean, L.J.H.; Stephens, K.; Amemiya, A., Eds.; University of Washington: Scattle, WA, 2017.
[37]
Gai, X.; Ghezzi, D.; Johnson, M.A.; Biagosch, C.A.; Shamseldin, H.E.; Haack, T.B.; Reyes, A.; Tsukikawa, M.; Sheldon, C.A.; Srinivasan, S.; Gorza, M.; Kremer, L.S.; Wieland, T.; Strom, T.M.; Polyak, E.; Place, E.; Consugar, M.; Ostrovsky, J.; Vidoni, S.; Robinson, A.J.; Wong, L.J.; Sondheimer, N.; Salih, M.A.; Al-Jishi, E.; Raab, C.P.; Bean, C.; Furlan, F.; Parini, R.; Lamperti, C.; Mayr, J.A.; Konstantopoulou, V.; Huemer, M.; Pierce, E.A.; Meitinger, T.; Freisinger, P.; Sperl, W.; Prokisch, H.; Alkuraya, F.S.; Falk, M.J.; Zeviani, M. Mutations in FBXL4, encoding a mitochondrial protein, cause early-onset mitochondrial encephalomyopathy. Am. J. Hum. Genet., 2013, 93, 482-495.
[38]
Huemer, M.; Karall, D.; Schossig, A.; Abdenur, J.E.; Al Jasmi, F.; Biagosch, C.; Distelmaier, F.; Freisinger, P.; Graham, B.H.; Haack, T.B. Hauser. N.; Hertecant, J.; Ebrahimi-Fakhari, D.; Konstantopoulou, V.; Leydiker, K.; Lourenco, C.M.; Scholl-Bürgi, S.; Wilichowski, E.; Wolf, N.I.; Wortmann, S.B.; Taylor, R.W.; Mayr, J.A.; Bonnen, P.E.; Sperl, W.; Prokisch, H.; McFarland, R. Clinical, morphological, biochemical, imaging and outcome parameters in 21 individuals with mitochondrial maintenance defect related to FBXL4 mutations. J. Inherit. Metab. Dis., 2015, 38, 905-914.
[39]
Baroy, T.; Pedurupillay, C.R.; Bliksrud, Y.T.; Rasmussen, M.; Holmgren, A.; Vigeland, M.D.; Hughes, T.; Brink, M. Rodenburg, R.; Nedregaard, B.; Strømme, P.; Frengen, E.; Misceo, D. A novel mutation in FBXL4 in a Norwegian child with encephalomyopathic mitochondrial DNA depletion syndrome 13. Eur. J. Med. Genet., 2016, 59, 342-346.
[40]
van Rij, M.C.; Jansen, F.A.; Hellebrekers, D.M.; Onkenhout, W.; Smeets, H.J.; Hendrickx, A.T.; Gottschalk, R.W.; Steggerda, S.J.; Peeters-Scholte, C.M.; Haak, M.C.; Hilhorst-Hofstee, Y. Polyhydramnios and cerebellar atrophy: A prenatal presentation of mitochondrial encephalomyopathy caused by mutations in the FBXL4 gene. Clin. Case Rep., 2016, 4, 425-428.
[41]
Bonnen, P.E.; Yarham, J.W.; Besse, A.; Wu, P.; Faqeih, E.A.; Al-Asmari, A.M.; Saleh, M.A.; Eyaid, W.; Hadeel, A.; He, L.; Smith, F.; Yau, S.; Simcox, E.M.; Miwa, S.; Donti, T.; Abu-Amero, K.K.; Wong, L.J.; Craigen, W.J.; Graham, B.H.; Scott, K.L.; McFarland, R.; Taylor, R.W. Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance. Am. J. Hum. Genet., 2013, 93, 471-481.
[42]
El-Hattab, A.W.; Dai, H.; Almannai, M.; Wang, J.; Faqeih, E.A.; Al Asmari, A.; Saleh, M.A.M.; Elamin, M.A.O.; Alfadhel, M.; Alkuraya, F.S. Hashem. M.; Aldosary, M.S.; Almass, R.; Almutairi, F.B.; Alsagob, M.; Al-Owain, M.; Al-Sharfa, S.; Al-Hassnan, Z.N.; Rahbeeni, Z.; Al-Muhaizea, M.A.; Makhseed, N.; Foskett, G.K.; Stevenson, D.A.; Gomez-Ospina, N.; Lee, C.; Boles, R.G.; Schrier Vergano, S.A.; Wortmann, S.B.; Sperl, W.; Opladen, T.; Hoffmann, G.F.; Hempel, M.; Prokisch, H.; Alhaddad, B.; Mayr, J.A.; Chan, W.; Kaya, N.; Wong, L.C. Molecular and clinical spectra of FBXL4 deficiency. Hum. Mutat., 2017, 38, 1649-1659.
[43]
Varela, I.; Tarpey, P.; Raine, K.; Huang, D.; Ong, C.K.; Stephens, P.; Davies, H.; Jones, D.; Lin, M.L.; Teague, J.; Bignell, G.; Butler, A.; Cho, J.; Dalgliesh, G.L.; Galappaththige, D.; Greenman, C.; Hardy, C.; Jia, M.; Latimer, C.; Lau, K.W.; Marshall, J.; McLaren, S.; Menzies, A.; Mudie, L.; Stebbings, L.; Largaespada, D.A.; Wessels, L.F.; Richard, S.; Kahnoski, R.J.; Anema, J.; Tuveson, D.A.; Perez-Mancera, P.A.; Mustonen, V.; Fischer, A.; Adams, D.J.; Rust, A.; Chan-on, W.; Subimerb, C.; Dykema, K.; Furge, K.; Campbell, P.J.; The, B.T.; Stratton, M.R.; Futreal, P.A. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature, 2011, 469, 539-542.
[44]
Kuchay, S.; Duan, S.; Schenkein, E.; Peschiaroli, A.; Saraf, A.; Florens, L.; Washburn, M.P.; Pagano, M. FBXL2- and PTPL1-mediated degradation of p110-free p85beta regulatory subunit controls the PI(3)K signalling cascade. Nat. Cell Biol., 2013, 15, 472-480.
[45]
Chen, B.B.; Glasser, J.R.; Coon, T.A.; Mallampalli, R.K. F-box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest. Oncogene, 2012, 31, 2566-2579.
[46]
Chen, B.B.; Glasser, J.R.; Coon, T.A.; Zou, C.; Miller, H.L.; Fenton, M.; McDyer, J.F.; Boyiadzis, M.; Mallampalli, R.K. F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation. Blood, 2012, 119, 3132-3141.
[47]
Xing, W.; Busino, L.; Hinds, T.R.; Marionni, S.T.; Saifee, N.H.; Bush, M.F.; Pagano, M.; Zheng, N. SCF(FBXL3) ubiquitin ligase targets cryptochromes at their cofactor pocket. Nature, 2013, 496, 64-68.
[48]
Sinibaldi, L.; De Luca, A.; Bellacchio, E.; Conti, E.; Pasini, A.; Paloscia, C.; Spalletta, G.; Caltagirone, C.; Pizzuti, A.; Dallapiccola, B. Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia. Hum. Mutat., 2004, 24, 534-535.
[49]
Hsu, R.; Woodroffe, A.; Lai, W.S.; Cook, M.N.; Mukai, J.; Dunning, J.P.; Swanson, D.J.; Roos, J.L.; Abecasis, G.R.; Karayiorgou, M.; Gogos, J.A. Nogo Receptor 1 (RTN4R) as a candidate gene for schizophrenia: Analysis using human and mouse genetic approaches. PLoS One, 2007, 2, e1234.
[50]
Budel, S.; Padukkavidana, T.; Liu, B.P.; Feng, Z.; Hu, F.; Johnson, S.; Lauren, J.; Park, J.H.; McGee, A.W.; Liao, J.; Stillman, A.; Kim, J.E.; Yang, B.Z.; Sodi, S.; Gelernter, J.; Zhao, H.; Hisama, F.; Arnsten, A.F.; Strittmatter, S.M. Genetic variants of Nogo-66 receptor with possible association to schizophrenia block myelin inhibition of axon growth. J. Neurosci., 2008, 28, 13161-13172.
[51]
Kimura, H.; Fujita, Y.; Kawabata, T.; Ishizuka, K.; Wang, C.; Iwayama, Y.; Okahisa, Y.; Kushima, I.; Morikawa, M.; Uno, Y.; Okada, T.; Ikeda, M.; Inada, T.; Branko, A.; Mori, D.; Yoshikawa, T.; Iwata, N.; Nakamura, H.; Yamashita, T.; Ozaki, N. A novel rare variant R292H in RTN4R affects growth cone formation and possibly contributes to schizophrenia susceptibility. Transl. Psychiatry, 2017, 7, e1214.
[52]
Lazar, N.L.; Singh, S.; Paton, T.; Clapcote, S.J.; Gondo, Y.; Fukumura, R.; Roder, J.C.; Cain, D.P. Missense mutation of the reticulon-4 receptor alters spatial memory and social interaction in mice. Behav. Brain Res., 2011, 224, 73-79.
[53]
Thomas, R.A.; Ambalavanan, A.; Rouleau, G.A.; Barker, P.A. Identification of genetic variants of LGI1 and RTN4R (NgR1) linked to schizophrenia that are defective in NgR1-LGI1 signaling. Mol. Genet. Genomic Med., 2016, 4, 447-456.
[54]
Nobile, C.; Michelucci, R.; Andreazza, S.; Pasini, E.; Tosatto, S.C.; Striano, P. LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy. Hum. Mutat., 2009, 30, 530-536.
[55]
Sirerol-Piquer, M.S.; Ayerdi-Izquierdo, A.; Morante-Redolat, J.M.; Herranz-Perez, V.; Favell, K.; Barker, P.A.; Perez-Tur, J. The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface. Hum. Mol. Genet., 2006, 15, 3436-3445.
[56]
Chabrol, E.; Popescu, C.; Gourfinkel-An, I.; Trouillard, O.; Depienne, C.; Senechal, K.; Baulac, M.; LeGuern, E.; Baulac, S. Two novel epilepsy-linked mutations leading to a loss of function of LGI1. Arch. Neurol., 2007, 64, 217-222.
[57]
Gu, W.; Brodtkorb, E.; Steinlein, O.K. LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures. Ann. Neurol., 2002, 52, 364-367.
[58]
Pizzuti, A.; Flex, E.; Di Bonaventura, C.; Dottorini, T.; Egeo, G.; Manfredi, M.; Dallapiccola, B.; Giallonardo, A.T. Epilepsy with auditory features: A LGI1 gene mutation suggests a loss-of-function mechanism. Ann. Neurol., 2003, 53, 396-399.
[59]
Berkovic, S.F.; Izzillo, P.; McMahon, J.M.; Harkin, L.A.; McIntosh, A.M.; Phillips, H.A.; Briellmann, R.S.; Wallace, R.H.; Mazarib, A.; Neufeld, M.Y.; Korczyn, A.D.; Scheffer, I.E.; Mulley, J.C. LGI1 mutations in temporal lobe epilepsies. Neurology, 2004, 62, 1115-1119.
[60]
Michelucci, R.; Mecarelli, O.; Bovo, G.; Bisulli, F.; Testoni, S.; Striano, P.; Striano, S.; Tinuper, P.; Nobile, C. A de novo LGI1 mutation causing idiopathic partial epilepsy with telephone-induced seizures. Neurology, 2007, 68, 2150-2151.
[61]
Striano, P.; de Falco, A.; Diani, E.; Bovo, G.; Furlan, S.; Vitiello, L.; Pinardi, F.; Striano, S.; Michelucci, R.; de Falco, F.A.; Nobile, C. A novel loss-of-function LGI1 mutation linked to autosomal dominant lateral temporal epilepsy. Arch. Neurol., 2008, 65, 939-942.
[62]
de Bellescize, J.; Boutry, N.; Chabrol, E.; Andre-Obadia, N.; Arzimanoglou, A.; Leguern, E.; Baulac, S.; Calender, A.; Ryvlin, P.; Lesca, G. A novel three base-pair LGI1 deletion leading to loss of function in a family with autosomal dominant lateral temporal epilepsy and migraine-like episodes. Epilepsy Res., 2009, 85, 118-122.
[63]
Di Bonaventura, C.; Carni, M.; Diani, E.; Fattouch, J.; Vaudano, E.A.; Egeo, G.; Pantano, P.; Maraviglia, B.; Bozzao, L.; Manfredi, M.; Prencipe, M.; Giallonardo, T.A.; Nobile, C. Drug resistant ADLTE and recurrent partial status epilepticus with dysphasic features in a family with a novel LGI1mutation: Electroclinical, genetic, and EEG/fMRI findings. Epilepsia, 2009, 50, 2481-2486.
[64]
Kalachikov, S.; Evgrafov, O.; Ross, B.; Winawer, M.; Barker-Cummings, C.; Martinelli Boneschi, F.; Choi, C.; Morozov, P.; Das, K.; Teplitskaya, E.; Yu, A.; Cayanis, E.; Penchaszadeh, G.; Kottmann, A.H.; Pedley, T.A.; Hauser, W.A.; Ottman, R.; Gilliam, T.C. Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features. Nat. Genet., 2002, 30, 335-341.
[65]
Ottman, R.; Winawer, M.R.; Kalachikov, S.; Barker-Cummings, C.; Gilliam, T.C.; Pedley, T.A.; Hauser, W.A. LGI1 mutations in autosomal dominant partial epilepsy with auditory features. Neurology, 2004, 62, 1120-1126.
[66]
Sadleir, L.G.; Agher, D.; Chabrol, E.; Elkouby, L.; Leguern, E.; Paterson, S.J.; Harty, R.; Bellows, S.T.; Berkovic, S.F.; Scheffer, I.E.; Baulac, S. Seizure semiology in autosomal dominant epilepsy with auditory features, due to novel LGI1 mutations. Epilepsy Res., 2013, 107, 311-317.
[67]
Di Bonaventura, C.; Operto, F.F.; Busolin, G.; Egeo, G.; D’Aniello, A.; Vitello, L.; Smaniotto, G.; Furlan, S.; Diani, E.; Michelucci, R.; Giallonardo, A.T.; Coppola, G.; Nobile, C. Low penetrance and effect on protein secretion of LGI1 mutations causing autosomal dominant lateral temporal epilepsy. Epilepsia, 2011, 52, 1258-1264.
[68]
Hedera, P.; Abou-Khalil, B.; Crunk, A.E.; Taylor, K.A.; Haines, J.L.; Sutcliffe, J.S. Autosomal dominant lateral temporal epilepsy: two families with novel mutations in the LGI1 gene. Epilepsia, 2004, 45, 218-222.
[69]
Pisano, T.; Marini, C.; Brovedani, P.; Brizzolara, D.; Pruna, D.; Mei, D.; Moro, F.; Cianchetti, C.; Guerrini, R. Abnormal phonologic processing in familial lateral temporal lobe epilepsy due to a new LGI1 mutation. Epilepsia, 2005, 46, 118-123.
[70]
Michelucci, R.; Poza, J.J.; Sofia, V.; de Feo, M.R.; Binelli, S.; Bisulli, F.; Scudellaro, E.; Simionati, B.; Zimbello, R.; D’Orsi, G.; Passarelli, D.; Avoni, P.; Avanzini, G.; Tinuper, P.; Biondi, R.; Valle, G.; Mautner, V.F.; Stephani, U. Autosomal dominant lateral temporal epilepsy: Clinical spectrum, new epitempin mutations, and genetic heterogeneity in seven European families. Epilepsia, 2003, 44, 1289-1297.
[71]
Klein, K.M.; Pendziwiat, M.; Cohen, R.; Appenzeller, S.; de Kovel, C.G.; Rosenow, F.; Koeleman, B.P.; Kuhlenbaumer, G.; Sheintuch, L.; Veksler, R.; Friedman, A.; Afawi, Z.; Helbig, I. Autosomal dominant epilepsy with auditory features: A new LGI1 family including a phenocopy with cortical dysplasia. J. Neurol., 2016, 263, 11-16.
[72]
Dazzo, E.; Santulli, L.; Posar, A.; Fattouch, J.; Conti, S.; Loden-van Straaten, M.; Mijalkovic, J.; De Bortoli, M.; Rosa, M.; Millino, C.; Pacchioni, B.; Di Bonaventura, C.; Giallonardo, A.T.; Striano, S.; Striano, P.; Parmeggiani, A.; Nobile, C. Autosomal dominant lateral temporal epilepsy (ADLTE): Novel structural and single-nucleotide LGI1 mutations in families with predominant visual auras. Epilepsy Res., 2015, 110, 132-138.
[73]
Fertig, E.; Lincoln, A.; Martinuzzi, A.; Mattson, R.H.; Hisama, F.M. Novel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features. Neurology, 2003, 60, 1687-1690.
[74]
Kawamata, J.; Ikeda, A.; Fujita, Y.; Usui, K.; Shimohama, S.; Takahashi, R. Mutations in LGI1 gene in Japanese families with autosomal dominant lateral temporal lobe epilepsy: The first report from Asian families. Epilepsia, 2010, 51, 690-693.
[75]
Heiman, G.A.; Kamberakis, K.; Gill, R.; Kalachikov, S.; Pedley, T.A.; Hauser, W.A.; Ottman, R. Evaluation of depression risk in LGI1 mutation carriers. Epilepsia, 2010, 51, 1685-1690.
[76]
Fumoto, N.; Matsumoto, R.; Kawamata, J.; Koyasu, S.; Kondo, T.; Kitamura, A.; Koshiba, Y.; Kinoshita, M.; Kawasaki, J.; Yamashita, H.; Takahashi, R.; Ikeda, A. Novel LGI1 mutation in a Japanese autosomal dominant lateral temporal lobe epilepsy family. Neurol. Clin. Neurosci., 2017, 5, 44-45.
[77]
Yokoi, N.; Fukata, Y.; Kase, D.; Miyazaki, T.; Jaegle, M.; Ohkawa, T.; Takahashi, N.; Iwanari, H.; Mochizuki, Y.; Hamakubo, T.; Imoto, K.; Meijer, D.; Watanabe, M.; Fukata, M. Chemical corrector treatment ameliorates increased seizure susceptibility in a mouse model of familial epilepsy. Nat. Med., 2015, 21, 19-26.
[78]
Matsubara, Y.; Murata, M.; Moriki, T.; Yokoyama, K.; Watanabe, N.; Nakajima, H.; Handa, M.; Kawano, K.; Aoki, N.; Yoshino, H.; Ikeda, Y. A novel polymorphism, 70Leu/Phe, disrupts a consensus Leu residue within the leucine-rich repeat sequence of platelet glycoprotein Ibalpha. Thromb. Haemost., 2002, 87, 867-872.
[79]
Matsubara, Y.; Murata, M.; Sugita, K.; Ikeda, Y. Identification of a novel point mutation in platelet glycoprotein Ibalpha, Gly to Ser at residue 233, in a Japanese family with platelet-type von Willebrand disease. J. Thromb. Haemost., 2003, 1, 2198-2205.
[80]
Murata, M.; Furihata, K.; Ishida, F.; Russell, S.R.; Ware, J.; Ruggeri, Z.M. Genetic and structural characterization of an amino acid dimorphism in glycoprotein Ib alpha involved in platelet transfusion refractoriness. Blood, 1992, 79, 3086-3090.
[81]
Miller, J.L.; Lyle, V.A.; Cunningham, D. Mutation of leucine-57 to phenylalanine in a platelet glycoprotein Ib alpha leucine tandem repeat occurring in patients with an autosomal dominant variant of Bernard-Soulier disease. Blood, 1992, 79, 439-446.
[82]
Ware, J.; Russell, S.R.; Marchese, P.; Murata, M.; Mazzucato, M.; De Marco, L.; Ruggeri, Z.M. Point mutation in a leucine-rich repeat of platelet glycoprotein Ib alpha resulting in the Bernard-Soulier syndrome. J. Clin. Invest., 1993, 92, 1213-1220.
[83]
Simsek, S.; Noris, P.; Lozano, M.; Pico, M.; von dem Borne, A.E.; Ribera, A.; Gallardo, D. Cys209 Ser mutation in the platelet membrane glycoprotein Ib alpha gene is associated with Bernard-Soulier syndrome. Br. J. Haematol., 1994, 88, 839-844.
[84]
Miller, J.L.; Cunningham, D.; Lyle, V.A.; Finch, C.N. Mutation in the gene encoding the alpha chain of platelet glycoprotein Ib in platelet-type von Willebrand disease. Proc. Natl. Acad. Sci. USA, 1991, 88, 4761-4765.
[85]
Murata, M.; Russell, S.R.; Ruggeri, Z.M.; Ware, J. Expression of the phenotypic abnormality of platelet-type von Willebrand disease in a recombinant glycoprotein Ib alpha fragment. J. Clin. Invest., 1993, 91, 2133-2137.
[86]
Russell, S.D.; Roth, G.J. Pseudo-von Willebrand disease: A mutation in the platelet glycoprotein Ib alpha gene associated with a hyperactive surface receptor. Blood, 1993, 81, 1787-1791.
[87]
Ishida, F.; Furihata, K.; Ishida, K.; Yan, J.; Kitano, K.; Kiyosawa, K.; Furuta, S. The largest variant of platelet glycoprotein Ib alpha has four tandem repeats of 13 amino acids in the macroglycopeptide region and a genetic linkage with methionine145. Blood, 1995, 86, 1357-1360.
[88]
de la Salle, C.; Baas, M.J.; Lanza, F.; Schwartz, A.; Hanau, D.; Chevalier, J.; Gachet, C.; Briquel, M.E.; Cazenave, J.P. A three-base deletion removing a leucine residue in a leucine-rich repeat of platelet glycoprotein Ib alpha associated with a variant of Bernard-Soulier syndrome (Nancy I). Br. J. Haematol., 1995, 89, 386-396.
[89]
Kenny, D.; Jonsson, O.G.; Morateck, P.A.; Montgomery, R.R. Naturally occurring mutations in glycoprotein Ibalpha that result in defective ligand binding and synthesis of a truncated protein. Blood, 1998, 92, 175-183.
[90]
Cargill, M.; Altshuler, D.; Ireland, J.; Sklar, P.; Ardlie, K.; Patil, N.; Shaw, N.; Lane, C.R.; Lim, E.P.; Kalyanaraman, N.; Nemesh, J.; Ziaugra, L.; Friedland, L.; Rolfe, A.; Warrington, J.; Lipshutz, R.; Daley, G.Q.; Lander, E.S. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat. Genet., 1999, 22, 231-238.
[91]
Koskela, S.; Partanen, J.; Salmi, T.T.; Kekomaki, R. Molecular characterization of two mutations in platelet glycoprotein (GP) Ib alpha in two Finnish Bernard-Soulier syndrome families. Eur. J. Haematol., 1999, 62, 160-168.
[92]
Savoia, A.; Balduini, C.L.; Savino, M.; Noris, P.; Del Vecchio, M.; Perrotta, S.; Belletti, S.; Poggi Iolascon, A. Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome. Blood, 2001, 97, 1330-1335.
[93]
Vettore, S.; Scandellari, R.; Moro, S.; Lombardi, A.M.; Scapin, M.; Randi, M.L.; Fabris, F. Novel point mutation in a leucine-rich repeat of the GPIbalpha chain of the platelet von Willebrand factor receptor, GPIb/IX/V, resulting in an inherited dominant form of Bernard-Soulier syndrome affecting two unrelated families: the N41H variant. Haematologica, 2008, 93, 1743-1747.
[94]
Yamamoto, N.; Akamatsu, N.; Sakuraba, H.; Matsuno, K.; Hosoya, R.; Nogami, H.; Kasahara, K.; Mitsuyama, S.; Arai, M. Novel Bernard-Soulier syndrome variants caused by compound heterozygous mutations (case I) or a cytoplasmic tail truncation (case II) of GPIbalpha. Thromb. Res., 2013, 131, e160-e167.
[95]
Savoia, A.; Kunishima, S.; De Rocco, D.; Zieger, B.; Rand, M.L.; Pujol-Moix, N.; Caliskan, U.; Tokgoz, H.; Pecci, A.; Noris, P.; Srivastava, A.; Ward, C.; Morel-Kopp, M.C.; Alessi, M.C.; Bellucci, S.; Beurrier, P.; de Maistre, E.; Favier, R.; Hézard, N.; Hurtaud-Roux, M.F.; Latger-Cannard, V.; Lavenu-Bombled, C.; Proulle, V.; Meunier, S.; Négrier, C.; Nurden, A.; Randrianaivo, H.; Fabris, F.; Platokouki, H.; Rosenberg, N. HadjKacem, B.; Heller, P.G.; Karimi, M.; Balduini, C.L.; Pastore, A.; Lanza, F. Spectrum of the mutations in Bernard-Soulier syndrome. Hum. Mutat., 35,, 033-1045,
[96]
Othman, M.; Emsley, J. Gene of the issue: GP1BA gene mutations associated with bleeding. Platelets, 2017, 28, 832-836.
[97]
Kunishima, S.; Lopez, J.A.; Kobayashi, S.; Imai, N.; Kamiya, T.; Saito, H.; Naoe, T. Missense mutations of the glycoprotein (GP) Ib beta gene impairing the GPIb alpha/beta disulfide linkage in a family with giant platelet disorder. Blood, 1997, 89, 2404-2412.
[98]
Kunishima, S.; Kamiya, T.; Saito, H. Genetic abnormalities of Bernard-Soulier syndrome. Int. J. Hematol., 2002, 76, 319-327.
[99]
Kunishima, S.; Naoe, T.; Kamiya, T.; Saito, H. Novel heterozygous missense mutation in the platelet glycoprotein Ib beta gene associated with isolated giant platelet disorder. Am. J. Hematol., 2001, 68, 249-255.
[100]
Kurokawa, Y.; Ishida, F.; Kamijo, T.; Kunishima, S.; Kenny, D.; Kitano, K.; Koike, K. A missense mutation (Tyr88 to Cys) in the platelet membrane glycoprotein Ibbeta gene affects GPIb/IX complex expression--Bernard-Soulier syndrome in the homozygous form and giant platelets in the heterozygous form. Thromb. Haemost., 2001, 86, 1249-1256.
[101]
Kunishima, S.; Imai, T.; Kobayashi, R.; Kato, M.; Ogawa, S.; Saito, H. Bernard-Soulier syndrome caused by a hemizygous GPIbbeta mutation and 22q11.2 deletion. Pediatr. Int., 2013, 55, 434-437.
[102]
Wright, S.D.; Michaelides, K.; Johnson, D.J.; West, N.C.; Tuddenham, E.G. Double heterozygosity for mutations in the platelet glycoprotein IX gene in three siblings with Bernard-Soulier syndrome. Blood, 1993, 81, 2339-2347.
[103]
Noris, P.; Simsek, S.; Stibbe, J.; von dem Borne, A.E. A phenylalanine-55 to serine amino-acid substitution in the human glycoprotein IX leucine-rich repeat is associated with Bernard-Soulier syndrome. Br. J. Haematol., 1997, 97, 312-320.
[104]
Noris, P.; Arbustini, E.; Spedini, P.; Belletti, S.; Balduini, C.L. A new variant of Bernard-Soulier syndrome characterized by dysfunctional glycoprotein (GP) Ib and severely reduced amounts of GPIX and GPV. Br. J. Haematol., 1998, 103, 1004-1013.
[105]
Kunishima, S.; Tomiyama, Y.; Honda, S.; Kurata, Y.; Kamiya, T.; Ozawa, K.; Saito, H. Cys97-->Tyr mutation in the glycoprotein IX gene associated with Bernard-Soulier syndrome. Br. J. Haematol., 1999, 107, 539-545.
[106]
Rivera, C.E.; Villagra, J.; Riordan, M.; Williams, S.; Lindstrom, K.J.; Rick, M.E. Identification of a new mutation in platelet glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome. Br. J. Haematol., 2001, 112, 105-108.
[107]
Wang, Z.; Shi, J.; Han, Y. A novel point mutation in the transmembrane domain of platelet glycoprotein IX gene identified in a Bernard-Soulier syndrome patient. Zhonghua Xue Ye Xue Za Zhi, 2001, 22, 464-466.
[108]
Boisseau, P.; Debord, C.; Eveillard, M.; Quemener, A.; Sigaud, M.; Giraud, M.; Talarmain, P.; Thomas, C.; Landeau, G.; Bezieau, S.; Petesch, B.P.; Béné, M.C.; Fouassier, M. Two novel variants of uncertain significance in GP9 associated with Bernard-Soulier syndrome: Are they true mutations? Platelets, 2018, 29(3), 316-318.
[109]
Miura, Y.; Mardy, S.; Awaya, Y.; Nihei, K.; Endo, F.; Matsuda, I.; Indo, Y. Mutation and polymorphism analysis of the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor in congenital insensitivity to pain with anhidrosis (CIPA) families. Hum. Genet., 2000, 106, 116-124.
[110]
Mardy, S.; Miura, Y.; Endo, F.; Matsuda, I.; Indo, Y. Congenital insensitivity to pain with anhidrosis (CIPA): Effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor. Hum. Mol. Genet., 2001, 10, 179-188.
[111]
Franco, M.L.; Melero, C.; Sarasola, E.; Acebo, P.; Luque, A.; Calatayud-Baselga, I.; Garcia-Barcina, M.; Vilar, M. Mutations in TrkA causing congenital insensitivity to pain with anhidrosis (CIPA) induce misfolding, aggregation, and mutation-dependent neurodegeneration by dysfunction of the autophagic flux. J. Biol. Chem., 2016, 291, 21363-21374.
[112]
Nam, T.S.; Li, W.; Yoon, S.; Eom, G.H.; Kim, M.K.; Jung, S.T.; Choi, S.Y. Novel NTRK1 mutations associated with congenital insensitivity to pain with anhidrosis verified by functional studies. J. Peripher. Nerv. Syst., 2017, 22, 92-99.
[113]
Altassan, R.; Saud, H.A.; Masoodi, T.A.; Dosssari, H.A.; Khalifa, O.; Al-Zaidan, H.; Sakati, N.; Rhabeeni, Z.; Al-Hassnan, Z.; Binamer, Y.; Alhashemi, N.; Wade, W.; Al-Zayed, Z.; Al-Sayed, M.; Al-Muhaizea, M.A.; Meyer, B.; Al-Owain, M.; Wakil, S.M. Exome sequencing identifies novel NTRK1 mutations in patients with HSAN-IV phenotype. Am. J. Med. Genet. A., 2017, 173, 1009-1016.
[114]
Greenman, C.; Stephens, P.; Smith, R.; Dalgliesh, G.L.; Hunter, C.; Bignell, G.; Davies, H.; Teague, J.; Butler, A.; Stevens, C.; Edkins, S.; O’Meara, S.; Vastrik, I.; Schmidt, E.E.; Avis, T.; Barthorpe, S.; Bhamra, G.; Buck, G.; Choudhury, B.; Clements, J.; Cole, J.; Dicks, E.; Forbes, S.; Gray, K.; Halliday, K.; Harrison, R.; Hills, K.; Hinton, J.; Jenkinson, A.; Jones, D.; Menzies, A.; Mironenko, T.; Perry, J.; Raine, K.; Richardson, D.; Shepherd, R.; Small, A.; Tofts, C.; Varian, J.; Webb, T.; West, S.; Widaa, S.; Yates, A.; Cahill, D.P.; Louis, D.N.; Goldstraw, P.; Nicholson, A.G.; Brasseur, F.; Looijenga, L.; Weber, B.L.; Chiew, Y.E.; DeFazio, A.; Greaves, M.F.; Green, A.R.; Campbell, P.; Birney, E.; Easton, D.F.; Chenevix-Trench, G.; Tan, M.H.; Khoo, S.K.; The, B.T.; Yuen, S.T.; Leung, S.Y.; Wooster, R.; Futreal, P.A.; Stratton, M.R. Patterns of somatic mutation in human cancer genomes. Nature, 2007, 446, 153-158.
[115]
Rossetti, S.; Chauveau, D.; Walker, D.; Saggar-Malik, A.; Winearls, C.G.; Torres, V.E.; Harris, P.C. A complete mutation screen of the ADPKD genes by DHPLC. Kidney Int., 2002, 61, 1588-1599.
[116]
Rossetti, S.; Chauveau, D.; Kubly, V.; Slezak, J.M.; Saggar-Malik, A.K.; Pei, Y.; Ong, A.C.; Stewart, F.; Watson, M.L.; Bergstralh, E.J.; Winearls, C.G.; Torres, V.E.; Harris, P.C. Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype. Lancet, 2003, 361, 2196-2201.
[117]
Hoefele, J.; Mayer, K.; Scholz, M.; Klein, H.G. Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD). Nephrol. Dial. Transplant., 2011, 26, 2181-2188.
[118]
Tan, Y.C.; Blumenfeld, J.D.; Anghel, R.; Donahue, S.; Belenkaya, R.; Balina, M.; Parker, T.; Levine, D.; Leonard, D.G.; Rennert, H. Novel method for genomic analysis of PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease. Hum. Mutat., 2009, 30, 264-273.
[119]
Rossetti, S.; Strmecki, L.; Gamble, V.; Burton, S.; Sneddon, V.; Peral, B.; Roy, S.; Bakkaloglu, A.; Komel, R.; Winearls, C.G.; Harris, P.C. Mutation analysis of the entire PKD1 gene: Genetic and diagnostic implications. Am. J. Hum. Genet., 2001, 68, 46-63.
[120]
Liu, B.; Chen, S.C.; Yang, Y.M.; Yan, K.; Qian, Y.Q.; Zhang, J.Y.; Hu, Y.T.; Dong, M.Y.; Jin, F.; Huang, H.F.; Xu, C.M. Identification of novel PKD1 and PKD2 mutations in a Chinese population with autosomal dominant polycystic kidney disease. Sci. Rep., 2015, 5, 17468.
[121]
De Leener, A.; Caltabiano, G.; Erkan, S.; Idil, M.; Vassart, G.; Pardo, L.; Costagliola, S. Identification of the first germline mutation in the extracellular domain of the follitropin receptor responsible for spontaneous ovarian hyperstimulation syndrome. Hum. Mutat., 2008, 29, 91-98.
[122]
Beau, I.; Touraine, P.; Meduri, G.; Gougeon, A.; Desroches, A.; Matuchansky, C.; Milgrom, E.; Kuttenn, F.; Misrahi, M. A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor. J. Clin. Invest., 1998, 102, 1352-1359.
[123]
Aittomaki, K.; Lucena, J.L.; Pakarinen, P.; Sistonen, P.; Tapanainen, J.; Gromoll, J.; Kaskikari, R.; Sankila, E.M.; Lehvaslaiho, H.; Engel, A.R.; Nieschlag, E.; Huhtaniemi, I.; de la Chapelle, A. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell, 1995, 82, 959-968.
[124]
Touraine, P.; Beau, I.; Gougeon, A.; Meduri, G.; Desroches, A.; Pichard, C.; Detoeuf, M.; Paniel, B.; Prieur, M.; Zorn, J.R.; Milgrom, E.; Kuttenn, F.; Misrahi, M. New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype. Mol. Endocrinol., 1999, 13, 1844-1854.
[125]
Allen, L.A.; Achermann, J.C.; Pakarinen, P.; Kotlar, T.J.; Huhtaniemi, I.T.; Jameson, J.L.; Cheetham, T.D.; Ball, S.G. A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotrophic hypogonadism: Clinical and molecular characteristics. Hum. Reprod., 2003, 18, 251-256.
[126]
Ulloa-Aguirre, A.; Zarinan, T. The follitropin receptor: Matching structure and function. Mol. Pharmacol., 2016, 90, 596-608.
[127]
Nakamura, Y.; Maekawa, R.; Yamagata, Y.; Tamura, I.; Sugino, N. A novel mutation in exon8 of the follicle-stimulating hormone receptor in a woman with primary amenorrhea. Gynecol. Endocrinol., 2008, 24, 708-712.
[128]
Ozcabi, B.; Tahmiscioglu Bucak, F.; Ceylaner, S.; Ozcan, R.; Buyukunal, C.; Ercan, O.; Tuysuz, B.; Evliyaoglu, O. Testotoxicosis: Report of two cases, one with a novel mutation in LHCGR gene. J. Clin. Res. Pediatr. Endocrinol., 2015, 7, 242-248.
[129]
Misrahi, M.; Meduri, G.; Pissard, S.; Bouvattier, C.; Beau, I.; Loosfelt, H.; Jolivet, A.; Rappaport, R.; Milgrom, E.; Bougneres, P. Comparison of immunocytochemical and molecular features with the phenotype in a case of incomplete male pseudoherma-phroditism associated with a mutation of the luteinizing hormone receptor. J. Clin. Endocrinol. Metab., 1997, 82, 2159-2165.
[130]
Richter-Unruh, A.; Verhoef-Post, M.; Malak, S.; Homoki, J.; Hauffa, B.P.; Themmen, A.P. Leydig cell hypoplasia: Absent luteinizing hormone receptor cell surface expression caused by a novel homozygous mutation in the extracellular domain. J. Clin. Endocrinol. Metab., 2004, 89, 5161-5167.
[131]
Qiao, J.; Han, B.; Liu, B.L.; Chen, X.; Ru, Y.; Cheng, K.X.; Chen, F.G.; Zhao, S.X.; Liang, J.; Lu, Y.L.; Tang, J.F.; Wu, Y.X.; Wu, W.L.; Chen, J.L.; Chen, M.D.; Song, H.D. A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism. Hum. Mutat., 2009, 30, E855-E865.
[132]
Martens, J.W.; Lumbroso, S.; Verhoef-Post, M.; Georget, V.; Richter-Unruh, A.; Szarras-Czapnik, M.; Romer, T.E.; Brunner, H.G.; Themmen, A.P.; Sultan, C. Mutant luteinizing hormone receptors in a compound heterozygous patient with complete Leydig cell hypoplasia: Abnormal processing causes signaling deficiency. J. Clin. Endocrinol. Metab., 2002, 87, 2506-2513.
[133]
Stavrou, S.S.; Zhu, Y.S.; Cai, L.Q.; Katz, M.D.; Herrera, C.; Defillo-Ricart, M.; Imperato-McGinley, J. A novel mutation of the human luteinizing hormone receptor in 46XY and 46XX sisters. J. Clin. Endocrinol. Metab., 1998, 83, 2091-2098.
[134]
Charmandari, E.; Guan, R.; Zhang, M.; Silveira, L.G.; Fan, Q.R.; Chrousos, G.P.; Sertedaki, A.C.; Latronico, A.C.; Segaloff, D.L. Misfolding ectodomain mutations of the lutropin receptor increase efficacy of hormone stimulation. Mol. Endocrinol., 2016, 30, 62-76.
[135]
Athanasoulia, A.P.; Stalla, G.K.; Auer, M.K. Insights into the coexistence of two mutations in the same LHCGR gene locus causing severe Leydig cell hypoplasia. Hormones (Athens), 2014, 13, 424-429.
[136]
Mitri, F.; Bentov, Y.; Behan, L.A.; Esfandiari, N.; Casper, R.F. A novel compound heterozygous mutation of the luteinizing hormone receptor -implications for fertility. J. Assist. Reprod. Genet., 2014, 31, 787-794.
[137]
Troppmann, B.; Kleinau, G.; Krause, G.; Gromoll, J. Structural and functional plasticity of the luteinizing hormone/ choriogonadotrophin receptor. Hum. Reprod. Update, 2013, 19, 583-602.
[138]
Leung, M.Y.; Steinbach, P.J.; Bear, D.; Baxendale, V.; Fechner, P.Y.; Rennert, O.M.; Chan, W.Y. Biological effect of a novel mutation in the third leucine-rich repeat of human luteinizing hormone receptor. Mol. Endocrinol., 2006, 20, 2493-2503.
[139]
Gromoll, J.; Schulz, A.; Borta, H.; Gudermann, T.; Teerds, K.J.; Greschniok, A.; Nieschlag, E.; Seif, F.J. Homozygous mutation within the conserved Ala-Phe-Asn-Glu-Thr motif of exon 7 of the LH receptor causes male pseudohermaphroditism. Eur. J. Endocrinol., 2002, 147, 597-608.
[140]
Ho, S.C.; Goh, S.S.; Khoo, D.H. Association of Graves’ disease with intragenic polymorphism of the thyrotropin receptor gene in a cohort of Singapore patients of multi-ethnic origins. Thyroid, 2003, 13, 523-528.
[141]
Peeters, R.P.; van Toor, H.; Klootwijk, W.; de Rijke, Y.B.; Kuiper, G.G.; Uitterlinden, A.G.; Visser, T.J. Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects. J. Clin. Endocrinol. Metab., 2003, 88, 2880-2888.
[142]
Tonacchera, M.; Perri, A.; De Marco, G.; Agretti, P.; Montanelli, L.; Banco, M.E.; Corrias, A.; Bellone, J.; Tosi, M.T.; Vitti, P.; Martino, E.; Pinchera, A.; Chiovato, L. TSH receptor and Gs(alpha) genetic analysis in children with Down’s syndrome and subclinical hypothyroidism. J. Endocrinol. Invest., 2003, 26, 997-1000.
[143]
de Roux, N.; Misrahi, M.; Brauner, R.; Houang, M.; Carel, J.C.; Granier, M.; Le Bouc, Y.; Ghinea, N.; Boumedienne, A.; Toublanc, J.E.; Milgrom, E. Four families with loss of function mutations of the thyrotropin receptor. J. Clin. Endocrinol. Metab., 1996, 81, 4229-4235.
[144]
Alberti, L.; Proverbio, M.C.; Costagliola, S.; Romoli, R.; Boldrighini, B.; Vigone, M.C.; Weber, G.; Chiumello, G.; Beck-Peccoz, P.; Persani, L. Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism. J. Clin. Endocrinol. Metab., 2002, 87, 2549-2555.
[145]
Clifton-Bligh, R.J.; Gregory, J.W.; Ludgate, M.; John, R.; Persani, L.; Asteria, C.; Beck-Peccoz, P.; Chatterjee, V.K. Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH. J. Clin. Endocrinol. Metab., 1997, 82, 1094-1100.
[146]
Tonacchera, M.; Perri, A.; De Marco, G.; Agretti, P.; Banco, M.E.; Di Cosmo, C.; Grasso, L.; Vitti, P.; Chiovato, L.; Pinchera, A. Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism. J. Clin. Endocrinol. Metab., 2004, 89, 5787-5793.
[147]
Sunthornthepvarakui, T.; Gottschalk, M.E.; Hayashi, Y.; Refetoff, S. Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene. N. Engl. J. Med., 1995, 332, 155-160.
[148]
Rodien, P.; Bremont, C.; Sanson, M.L.; Parma, J.; Van Sande, J.; Costagliola, S.; Luton, J.P.; Vassart, G.; Duprez, L. Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotropin. N. Engl. J. Med., 1998, 339, 1823-1826.
[149]
Kopp, P.; Muirhead, S.; Jourdain, N.; Gu, W.X.; Jameson, J.L.; Rodd, C. Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor. J. Clin. Invest., 1997, 100, 1634-1639.
[150]
Ohno, M.; Endo, T.; Ohta, K.; Gunji, K.; Onaya, T. Point mutations in the thyrotropin receptor in human thyroid tumors. Thyroid, 1995, 5, 97-100.
[151]
Parma, J.; Duprez, L.; Van Sande, J.; Hermans, J.; Rocmans, P.; Van Vliet, G.; Costagliola, S.; Rodien, P.; Dumont, J.E.; Vassart, G. Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas. J. Clin. Endocrinol. Metab., 1997, 82, 2695-2701.
[152]
Russo, D.; Betterle, C.; Arturi, F.; Chiefari, E.; Girelli, M.E.; Filetti, S. A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH. J. Clin. Endocrinol. Metab., 2000, 85, 4238-4242.
[153]
Bech-Hansen, N.T.; Naylor, M.J.; Maybaum, T.A.; Sparkes, R.L.; Koop, B.; Birch, D.G.; Bergen, A.A.; Prinsen, C.F.; Polomeno, R.C.; Gal, A.; Drack, A.V.; Musarella, M.A.; Jacobson, S.G.; Young, R.S.; Weleber, R.G. Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness. Nat. Genet., 2000, 26, 319-323.
[154]
Pusch, C.M.; Zeitz, C.; Brandau, O.; Pesch, K.; Achatz, H.; Feil, S.; Scharfe, C.; Maurer, J.; Jacobi, F.K.; Pinckers, A.; Andreasson, S.; Hardcastle, A.; Wissinger, B.; Berger, W.; Meindl, A. The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein. Nat. Genet., 2000, 26, 324-327.
[155]
Zhou, L.; Li, T.; Song, X.; Li, Y.; Li, H.; Dan, H. NYX mutations in four families with high myopia with or without CSNB1. Mol. Vis., 2015, 21, 213-223.
[156]
Leroy, B.P.; Budde, B.S.; Wittmer, M.; De Baere, E.; Berger, W.; Zeitz, C. A common NYX mutation in Flemish patients with X linked CSNB. Br. J. Ophthalmol., 2009, 93, 692-696.
[157]
Dai, S.; Ying, M.; Wang, K.; Wang, L.; Han, R.; Hao, P.; Li, N. Two novel NYX gene mutations in the chinese families with X-linked congenital stationary night blindness. Sci. Rep., 2015, 5, 12679.
[158]
Pradhan, M.; Sharp, D.; Mora, J.; Wittmer, M.; Berger, W.; Vincent, A. A novel NYX mutation associated with X-linked congenital stationary night blindness in a New Zealand family. J. Clinic. Expermiment Oohthamol., 2011, 2, 1-4.
[159]
Wang, Q.; Gao, Y.; Li, S.; Guo, X.; Zhang, Q. Mutation screening of TRPM1, GRM6, NYX and CACNA1F genes in patients with congenital stationary night blindness. Int. J. Mol. Med., 2012, 30, 521-526.
[160]
Xiao, X.; Jia, X.; Guo, X.; Li, S.; Yang, Z.; Zhang, Q. CSNB1 in Chinese families associated with novel mutations in NYX. J. Hum. Genet., 2006, 51, 634-640.
[161]
Zeitz, C.; Minotti, R.; Feil, S.; Matyas, G.; Cremers, F.P.; Hoyng, C.B.; Berger, W. Novel mutations in CACNA1F and NYX in Dutch families with X-linked congenital stationary night blindness. Mol. Vis., 2005, 11, 179-183.
[162]
Sui, R.; Li, F.; Zhao, J.; Jiang, R. Clinical and genetic characterization of a Chinese family with CSNB1. Adv. Exp. Med. Biol., 2008, 613, 245-252.
[163]
Yip, S.P.; Li, C.C.; Yiu, W.C.; Hung, W.H.; Lam, W.W.; Lai, M.C.; Ng, P.W.; Fung, W.Y.; Chu, P.H.; Jiang, B.; Chan, H.H.; Yap, M.K. A novel missense mutation in the NYX gene associated with high myopia. Ophthalmic Physiol. Opt., 2013, 33, 346-353.
[164]
Zhang, Q.; Xiao, X.; Li, S.; Jia, X.; Yang, Z.; Huang, S.; Caruso, R.C.; Guan, T.; Sergeev, Y.; Guo, X.; Hejtmancik, J.F. Mutations in NYX of individuals with high myopia, but without night blindness. Mol. Vis., 2007, 13, 330-336.
[165]
Zeitz, C.; Jacobson, S.G.; Hamel, C.P.; Bujakowska, K.; Neuille, M.; Orhan, E.; Zanlonghi, X.; Lancelot, M.E.; Michiels, C.; Schwartz, S.B.; Bocquet, B.; Congenital Stationary Night Blindness Consortium; Antonio, A.; Audier, C.; Letexier, M.; Saraiva, J.P.; Luu, T.D.; Sennlaub, F.; Nguyen, H.; Poch, O.; Dollfus, H.; Lecompte, O.; Kohl, S.; Sahel, J.A.; Bhattacharya, S.S.; Audo, I. Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness. Am. J. Hum. Genet., 2013, 92, 67-75.
[166]
Dan, H.; Song, X.; Li, J.; Xing, Y.; Li, T. Mutation screening of the LRIT3, CABP4, and GPR179 genes in Chinese patients with Schubert-Bornschein congenital stationary night blindness. Ophthalmic Genet., 2017, 38, 206-210.
[167]
Zeitz, C.; Robson, A.G.; Audo, I. Congenital stationary night blindness: an analysis and update of genotype-phenotype correlations and pathogenic mechanisms. Prog. Retin. Eye Res., 2015, 45, 58-110.
[168]
Gorlov, I.P.; Kamat, A.; Bogatcheva, N.V.; Jones, E.; Lamb, D.J.; Truong, A.; Bishop, C.E.; McElreavey, K.; Agoulnik, A.I. Mutations of the GREAT gene cause cryptorchidism. Hum. Mol. Genet., 2002, 11, 2309-2318.
[169]
Bogatcheva, N.V.; Ferlin, A.; Feng, S.; Truong, A.; Gianesello, L.; Foresta, C.; Agoulnik, A.I. T222P mutation of the insulin-like 3 hormone receptor LGR8 is associated with testicular maldescent and hinders receptor expression on the cell surface membrane. Am. J. Physiol. Endocrinol. Metab., 2007, 292, E138-E144.
[170]
Fofanova-Gambetti, O.V.; Hwa, V.; Kirsch, S.; Pihoker, C.; Chiu, H.K.; Hogler, W.; Cohen, L.E.; Jacobsen, C.; Derr, M.A.; Rosenfeld, R.G. Three novel IGFALS gene mutations resulting in total ALS and severe circulating IGF-I/IGFBP-3 deficiency in children of different ethnic origins. Horm. Res., 2009, 71, 100-110.
[171]
David, A.; Rose, S.J.; Miraki-Moud, F.; Metherell, L.A.; Savage, M.O.; Clark, A.J.; Camacho-Hubner, C. Acid-labile subunit deficiency and growth failure: Description of two novel cases. Horm. Res. Paediatr., 2010, 73, 328-334.
[172]
Hess, O.; Khayat, M.; Hwa, V.; Heath, K.E.; Teitler, A.; Hritan, Y.; Allon-Shalev, S.; Tenenbaum-Rakover, Y. A novel mutation in IGFALS, c.380T>C (p.L127P), associated with short stature, delayed puberty, osteopenia and hyperinsulinaemia in two siblings: Insights into the roles of insulin growth factor-1 (IGF1). Clin. Endocrinol. (Oxf.), 2013, 79, 838-844.
[173]
Domene, H.M.; Scaglia, P.A.; Lteif, A.; Mahmud, F.H.; Kirmani, S.; Frystyk, J.; Bedecarras, P.; Gutierrez, M.; Jasper, H.G. Phenotypic effects of null and haploinsufficiency of acid-labile subunit in a family with two novel IGFALS gene mutations. J. Clin. Endocrinol. Metab., 2007, 92, 4444-4450.
[174]
Heath, K.E.; Argente, J.; Barrios, V.; Pozo, J.; Diaz-Gonzalez, F.; Martos-Moreno, G.A.; Caimari, M.; Gracia, R.; Campos-Barros, A. Primary acid-labile subunit deficiency due to recessive IGFALS mutations results in postnatal growth deficit associated with low circulating insulin growth factor (IGF)-I, IGF binding protein-3 levels, and hyperinsulinemia. J. Clin. Endocrinol. Metab., 2008, 93, 1616-1624.
[175]
Hwa, V.; Haeusler, G.; Pratt, K.L.; Little, B.M.; Frisch, H.; Koller, D.; Rosenfeld, R.G. Total absence of functional acid labile subunit, resulting in severe insulin-like growth factor deficiency and moderate growth failure. J. Clin. Endocrinol. Metab., 2006, 91, 1826-1831.
[176]
Scaglia, P.A.; Keselman, A.C.; Braslavsky, D.; Martucci, L.C.; Karabatas, L.M.; Domene, S.; Gutierrez, M.L.; Ballerini, M.G.; Ropelato, M.G.; Spinola-Castro, A.; Siviero-Miachon, A.A.; Tartuci, J.S.; Rodríguez Azrak, M.S.; Rey, R.A.; Jasper, H.G.; Bergadá, I.; Domené, H.M. Characterization of four Latin American families confirms previous findings and reveals novel features of acid-labile subunit deficiency. Clin. Endocrinol. (Oxf.), 2017, 87, 300-311.
[177]
Schreiner, F.; Schoenberger, S.; Koester, B.; Domene, H.M.; Woelfle, J. Novel acid-labile subunit (IGFALS) mutation p.T145K (c.434C>A) in a patient with ALS deficiency, normal stature and immunological dysfunction. Horm. Res. Paediatr., 2013, 80, 424-430.
[178]
Kang, H.; Han, K.A.; Won, S.Y.; Kim, H.M.; Lee, Y.H.; Ko, J.; Um, J.W. Slitrk Missense Mutations associated with neuropsychiatric disorders distinctively impair slitrk trafficking and synapse formation. Front. Mol. Neurosci., 2016, 9, 104.
[179]
Ozomaro, U.; Cai, G.; Kajiwara, Y.; Yoon, S.; Makarov, V.; Delorme, R.; Betancur, C.; Ruhrmann, S.; Falkai, P.; Grabe, H.J.; Maier, W.; Wagner, M.; Lennertz, L.; Moessner, R.; Murphy, D.L.; Buxbaum, J.D.; Züchner, S.; Grice, D.E. Characterization of SLITRK1 variation in obsessive-compulsive disorder. PLoS One, 2013, 8, e70376.
[180]
Piton, A.; Gauthier, J.; Hamdan, F.F.; Lafreniere, R.G.; Yang, Y.; Henrion, E.; Laurent, S.; Noreau, A.; Thibodeau, P. Karemera. L.; Spiegelman, D.; Kuku, F.; Duguay, J.; Destroismaisons, L.; Jolivet, P.; Côté, M.; Lachapelle, K.; Diallo, O.; Raymond, A.; Marineau, C.; Champagne, N.; Xiong, L.; Gaspar, C.; Rivière, J.B.; Tarabeux, J.; Cossette, P.; Krebs, M.O.; Rapoport, J.L.; Addington, A.; Delisi, L.E.; Mottron, L.; Joober, R.; Fombonne, E.; Drapeau, P.; Rouleau, G.A. Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia. Mol. Psychiatry, 2011, 16, 867-880.
[181]
Song, M.; Mathews, C.A.; Stewart, S.E.; Shmelkov, S.V.; Mezey, J.G.; Rodriguez-Flores, J.L.; Rasmussen, S.A.; Britton, J.C.; Oh, Y.S.; Walkup, J.T.; Lee, F.S.; Glatt, C.E. Rare synaptogenesis-impairing mutations in SLITRK5 are associated with obsessive compulsive disorder. PLoS One, 2017, 12, e0169994.
[182]
Xiong, D.; Li, G. Li.; K, Xu.; Q, Pan.; Z, Ding.; F, Vedell, P.; Liu, P.; Cui, P.; Hua, X.; Jiang, H.; Yin, Y.; Zhu, Z.; Li, X.; Zhang, B.; Ma, D.; Wang, Y.; You, M. Exome sequencing identifies MXRA5 as a novel cancer gene frequently mutated in non-small cell lung carcinoma from Chinese patients. Carcinogenesis, 2012, 33, 1797-1805.
[183]
Arbour, N.C.; Lorenz, E.; Schutte, B.C.; Zabner, J.; Kline, J.N.; Jones, M.; Frees, K.; Watt, J.L.; Schwartz, D.A. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat. Genet., 2000, 25, 187-191.
[184]
Zareparsi, S.; Buraczynska, M.; Branham, K.E.; Shah, S.; Eng, D.; Li, M.; Pawar, H.; Yashar, B.M.; Moroi, S.E.; Lichter, P.R.; Petty, H.R.; Richards, J.E.; Abecasis, G.R.; Elner, V.M.; Swaroop, A. Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration. Hum. Mol. Genet., 2005, 14, 1449-1455.
[185]
Franchimont, D.; Vermeire, S.; El Housni, H.; Pierik, M.; Van Steen, K.; Gustot, T.; Quertinmont, E.; Abramowicz, M.; Van Gossum, A.; Deviere, J.; Rutgeerts, P. Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis. Gut, 2004, 53, 987-992.
[186]
Oostenbrug, L.E.; Drenth, J.P.; de Jong, D.J.; Nolte, I.M.; Oosterom, E.; van Dullemen, H.M.; van der Linde, K.; te Meerman, G.J.; van der Steege, G.; Kleibeuker, J.H.; Jansen, P.L. Association between Toll-like receptor 4 and inflammatory bowel disease. Inflamm. Bowel Dis., 2005, 11, 567-575.
[187]
Browning, B.L.; Huebner, C.; Petermann, I.; Gearry, R.B.; Barclay, M.L.; Shelling, A.N.; Ferguson, L.R. Has toll-like receptor 4 been prematurely dismissed as an inflammatory bowel disease gene? Association study combined with meta-analysis shows strong evidence for association. Am. J. Gastroenterol., 2007, 102, 2504-2512.
[188]
De Jager, P.L.; Franchimont, D.; Waliszewska, A.; Bitton, A.; Cohen, A.; Langelier, D.; Belaiche, J.; Vermeire, S.; Farwell, L.; Goris, A.; Libioulle, C.; Jani, N.; Dassopoulos, T.; Bromfield, G.P.; Dubois, B.; Cho, J.H.; Brant, S.R.; Duerr, R.H.; Yang, H.; Rotter, J.I.; Silverberg, M.S.; Steinhart, A.H.; Daly, M.J.; Podolsky, D.K.; Louis, E.; Hafler, D.A.; Rioux, J.D. Quebec IBD Genetics Consortium NIDDK IBD Genetics Consortium. The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases. Genes Immun., 2007, 8, 387-397.
[189]
Meena, N.K.; Ahuja, V.; Meena, K.; Paul, J. Association of TLR5 gene polymorphisms in ulcerative colitis patients of north India and their role in cytokine homeostasis. PLoS One, 2015, 10, e0120697.
[190]
Sales, M.L.; Schreiber, R.; Ferreira-Sae, M.C.; Fernandes, M.N.; Piveta, C.S.; Cipolli, J.A.; Cardoso, C.C.; Matos-Souza, J.R.; Geloneze, B.; Franchini, K.G.; Nadruz, W., Jr Toll-like receptor 6 Ser249Pro polymorphism is associated with lower left ventricular wall thickness and inflammatory response in hypertensive women. Am. J. Hypertens., 2010, 23, 649-654.
[191]
Uff, S.; Clemetson, J.M.; Harrison, T.; Clemetson, K.J.; Emsley, J. (2002) Crystal structure of the platelet glycoprotein Ib alpha N-terminal domain reveals an unmasking mechanism for receptor activation. J. Biol. Chem., 2002, (277), 35657-35663.
[192]
Kumari, D.; Tiwari, A.; Choudhury, M.; Kumar, A.; Rao, A.; Dixit, M. A novel KERA mutation in a case of autosomal recessive cornea plana with primary angle-closure glaucoma. J. Glaucoma, 2016, 25, e106-e109.
[193]
Ebenezer, N.D.; Patel, C.B.; Hariprasad, S.M.; Chen, L.L.; Patel, R.J.; Hardcastle, A.J.; Allen, R.C. Clinical and molecular characterization of a family with autosomal recessive cornea plana. Arch. Ophthalmol., 2005, 123, 1248-1253.
[194]
Lehmann, O.J.; El-ashry, M.F.; Ebenezer, N.D.; Ocaka, L.; Francis, P.J.; Wilkie, S.E.; Patel, R.J.; Ficker, L.; Jordan, T.; Khaw, P.T.; Bhattacharya, S.S. A novel keratocan mutation causing autosomal recessive cornea plana. Invest. Ophthalmol. Vis. Sci., 2001, 42, 3118-3122.
[195]
Pellegata, N.S.; Dieguez-Lucena, J.L.; Joensuu, T.; Lau, S.; Montgomery, K.T.; Krahe, R.; Kivela, T.; Kucherlapati, R.; Forsius, H.; de la Chapelle, A. Mutations in KERA, encoding keratocan, cause cornea plana. Nat. Genet., 2000, 25, 91-95.
[196]
Roos, L.; Bertelsen, B.; Harris, P.; Bygum, A.; Jensen, H.; Gronskov, K.; Tumer, Z. Case report: A novel KERA mutation associated with cornea plana and its predicted effect on protein function. BMC Med. Genet., 2015, 16, 40.
[197]
Dudakova, L.; Vercruyssen, J.H.J.; Balikova, I.; Postolache, L.; Leroy, B.P.; Skalicka, P.; Liskova, P. Analysis of KERA in four families with cornea plana identifies two novel mutations. Acta Ophthalmol., 2018, 96, e87-e91.
[198]
Wang, P.; Li, S.; Xiao, X.; Guo, X.; Zhang, Q. An evaluation of OPTC and EPYC as candidate genes for high myopia. Mol. Vis., 2009, 15, 2045-2049.
[199]
Majava, M.; Bishop, P.N.; Hagg, P.; Scott, P.G.; Rice, A.; Inglehearn, C.; Hammond, C.J.; Spector, T.D.; Ala-Kokko, L.; Mannikko, M. Novel mutations in the small leucine-rich repeat protein/proteoglycan (SLRP) genes in high myopia. Hum. Mutat., 2007, 28, 336-344.
[200]
Acharya, M.; Mookherjee, S.; Bhattacharjee, A.; Thakur, S.K.; Bandyopadhyay, A.K.; Sen, A.; Chakrabarti, S.; Ray, K. Evaluation of the OPTC gene in primary open angle glaucoma: Functional significance of a silent change. BMC Mol. Biol., 2007, 8, 21.
[201]
Cho, S.Y.; Bae, J.S.; Kim, N.K.D.; Forzano, F.; Girisha, K.M.; Baldo, C.; Faravelli, F.; Cho, T.J.; Kim, D.; Lee, K.Y.; Ikegawa, S.; Shim, J.S.; Ko, A.R.; Miyake, N.; Nishimura, G.; Superti-Furga, A.; Spranger, J.; Kim, O.H.; Park, W.Y.; Jin, D.K. BGN mutations in X-linked spondyloepimetaphyseal dysplasia. Am. J. Hum. Genet., 2016, 98, 1243-1248.
[202]
Meester, J.A.; Vandeweyer, G.; Pintelon, I.; Lammens, M.; Van Hoorick, L.; De Belder, S.; Waitzman, K.; Young, L.; Markham, L.W.; Vogt, J.; Richer, J.; Beauchesne, L.M.; Unger, S.; Superti-Furga, A.; Prsa, M.; Dhillon, R.; Reyniers, E.; Dietz, H.C.; Wuyts, W.; Mortier, G.; Verstraeten, A.; Van Laer, L.; Loeys, B.L. Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections. Genet. Med., 2017, 19, 386-395.
[203]
Miraoui, H.; Dwyer, A.A.; Sykiotis, G.P.; Plummer, L.; Chung, W.; Feng, B.; Beenken, A.; Clarke, J.; Pers, T.H.; Dworzynski, P.; Keefe, K.; Niedziela, M.; Raivio, T.; Crowley, W.F., Jr; Seminara, S.B.; Quinton, R.; Hughes, V.A.; Kumanov, P.; Young, J.; Yialamas, M.A.; Hall, J.E.; Van Vliet, G.; Chanoine, J.P.; Rubenstein, J.; Mohammadi, M.; Tsai, P.S.; Sidis, Y.; Lage, K.; Pitteloud, N. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am. J. Hum. Genet., 2013, 92, 725-743.
[204]
Matsushima, N.; Ohyanagi, T.; Tanaka, T.; Kretsinger, R.H. Super-motifs and evolution of tandem leucine-rich repeats within the small proteoglycans--biglycan, decorin, lumican, fibromodulin, PRELP, keratocan, osteoadherin, epiphycan, and osteoglycin. Proteins, 2000, 38, 210-225.
[205]
Batkhishig, D.; Bilguun, K.; Enkhbayar, P.; Miyashita, H.; Kretsinger, R.H.; Matsushima, N. Super secondary structure consisting of a polyproline ii helix and a beta-turn in leucine rich repeats in bacterial Type III secretion system effectors. Protein J., 2018, 37, 223-236.
[206]
Garavelli, L.; Cordeddu, V.; Errico, S.; Bertolini, P.; Street, M.E.; Rosato, S.; Pollazzon, M.; Wischmeijer, A.; Ivanovski, I.; Daniele, P.; Bacchini, E.; Lombardi, A.A.; Izzi, G.; Biasucci, G.; Del Rossi, C.; Corradi, D.; Cazzaniga, G.; Dominici, C.; Rossi, C.; De Luca, A.; Bernasconi, S.; Riccardi, R.; Legius, E.; Tartaglia, M. Noonan syndrome-like disorder with loose anagen hair: A second case with neuroblastoma. Am. J. Med. Genet. A., 2015, 167A, 1902-1907.
[207]
Lo, F.S.; Wang, C.J.; Wong, M.C.; Lee, N.C. Moyamoya disease in two patients with Noonan-like syndrome with loose anagen hair. Am. J. Med. Genet. A., 2015, 167, 1285-1288.
[208]
Brody, M.J.; Lee, Y. The role of leucine-rich repeat containing protein 10 (LRRC10) in Dilated Cardiomyopathy. Front. Physiol., 2016, 7, 337.
[209]
Qu, X.K.; Yuan, F.; Li, R.G.; Xu, L.; Jing, W.F.; Liu, H.; Xu, Y.J.; Zhang, M.; Liu, X.; Fang, W.Y.; Yang, Y.Q.; Qiu, X.B. Prevalence and spectrum of LRRC10 mutations associated with idiopathic dilated cardiomyopathy. Mol. Med. Rep., 2015, 12, 3718-3724.
[210]
Woon, M.T.; Long, P.A.; Reilly, L.; Evans, J.M.; Keefe, A.M.; Lea, M.R.; Beglinger, C.J.; Balijepalli, R.C.; Lee, Y.; Olson, T.M.; Kamp, T.J. Pediatric dilated cardiomyopathy-associated LRRC10 (Leucine-Rich Repeat-Containing 10) variant reveals LRRC10 as an auxiliary subunit of cardiac L-Type Ca2+ channels. J. Am. Heart Assoc., 2018, 7, e006428.
[211]
Huang, L.; Tang, S.; Chen, Y.; Zhang, L.; Yin, K.; Wu, Y.; Zheng, J.; Wu, Q.; Makielski, J.C.; Cheng, J. Molecular pathological study on LRRC10 in sudden unexplained nocturnal death syndrome in the Chinese Han population. Int. J. Legal Med., 2017, 131, 621-628.
[212]
Miras, I.; Saul, F.; Nowakowski, M.; Weber, P.; Haouz, A.; Shepard, W.; Picardeau, M. Structural characterization of a novel subfamily of leucine-rich repeat proteins from the human pathogen Leptospira interrogans. Acta Crystallogr. D Biol. Crystallogr., 2015, 71, 1351-1359.
[213]
Mazor, M.; Alkrinawi, S.; Chalifa-Caspi, V.; Manor, E.; Sheffield, V.C.; Aviram, M.; Parvari, R. Primary ciliary dyskinesia caused by homozygous mutation in DNAL1, encoding dynein light chain 1. Am. J. Hum. Genet., 2011, 88, 599-607.
[214]
Duquesnoy, P.; Escudier, E.; Vincensini, L.; Freshour, J.; Bridoux, A.M.; Coste, A.; Deschildre, A.; de Blic, J.; Legendre, M.; Montantin, G.; Tenreiro, H.; Vojtek, A.M.; Loussert, C.; Clément, A.; Escalier, D.; Bastin, P.; Mitchell, D.R.; Amselem, S. Loss-of-function mutations in the human ortholog of Chlamydomonas reinhardtii ODA7 disrupt dynein arm assembly and cause primary ciliary dyskinesia. Am. J. Hum. Genet., 2009, 85, 890-896.
[215]
Raidt, J.; Wallmeier, J.; Hjeij, R.; Onnebrink, J.G.; Pennekamp, P.; Loges, N.T.; Olbrich, H.; Haffner, K.; Dougherty, G.W.; Omran, H.; Werner, C. Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia. Eur. Respir. J., 2014, 44, 1579-1588.
[216]
Loges, N.T.; Olbrich, H.; Becker-Heck, A.; Haffner, K.; Heer, A.; Reinhard, C.; Schmidts, M.; Kispert, A.; Zariwala, M.A.; Leigh, M.W.; Knowles, M.R.; Zentgraf, H.; Seithe, H.; Nürnberg, G.; Nürnberg, P.; Reinhardt, R.; Omran, H. Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects. Am. J. Hum. Genet., 2009, 85, 883-889.
[217]
Kott, E.; Duquesnoy, P.; Copin, B.; Legendre, M.; Dastot-Le Moal, F.; Montantin, G.; Jeanson, L.; Tamalet, A.; Papon, J.F.; Siffroi, J.P. Rives, N.; Mitchell, V.; de Blic, J.; Coste, A.; Clement, A.; Escalier, D.; Touré, A.; Escudier, E.; Amselem, S. Loss-of-function mutations in LRRC6, a gene essential for proper axonemal assembly of inner and outer dynein arms, cause primary ciliary dyskinesia. Am. J. Hum. Genet., 2012, 91, 958-964.
[218]
Horani, A.; Ferkol, T.W.; Shoseyov, D.; Wasserman, M.G.; Oren, Y.S.; Kerem, B.; Amirav, I.; Cohen-Cymberknoh, M.; Dutcher, S.K.; Brody, S.L.; Elpeleg, O.; Kerem, E. LRRC6 mutation causes primary ciliary dyskinesia with dynein arm defects. PLoS One, 2013, 8, e59436.
[219]
Liu, L.; Luo, H. Whole-exome sequencing identified a novel compound heterozygous mutation of LRRC6 in a chinese primary ciliary dyskinesia patient. BioMed Res. Int., 2018, 2018, 1854269.
[220]
Skipper, L.; Shen, H.; Chua, E.; Bonnard, C.; Kolatkar, P.; Tan, L.C.; Jamora, R.D.; Puvan, K.; Puong, K.Y.; Zhao, Y.; Pavanni, R.; Wong, M.C.; Yuen, Y.; Farrer, M.; Liu, J.J.; Tan, E.K. Analysis of LRRK2 functional domains in nondominant Parkinson disease. Neurology, 2005, 65, 1319-1321.
[221]
Berg, D.; Schweitzer, K.J.; Leitner, P.; Zimprich, A.; Lichtner, P.; Belcredi, P.; Brussel, T.; Schulte, C.; Maass, S.; Nagele, T.; Wszolek, Z.K.; Gasser, T. Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson’s disease. Brain, 2005, 128, 3000-3011.
[222]
Zimprich, A.; Biskup, S.; Leitner, P.; Lichtner, P.; Farrer, M.; Lincoln, S.; Kachergus, J.; Hulihan, M.; Uitti, R.J.; Calne, D.B.; Stoessl, A.J.; Pfeiffer, R.F.; Patenge, N.; Carbajal, I.C.; Vieregge, P.; Asmus, F.; Müller-Myhsok, B.; Dickson, D.W.; Meitinger, T.; Strom, T.M.; Wszolek, Z.K.; Gasser, T. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron, 2004, 44, 601-607.
[223]
Nichols, W.C.; Elsaesser, V.E.; Pankratz, N.; Pauciulo, M.W.; Marek, D.K.; Halter, C.A.; Rudolph, A.; Shults, C.W.; Foroud, T. Parkinson Study Group PI: LRRK2 mutation analysis in Parkinson disease families with evidence of linkage to PARK8. Neurology, 2007, 69, 1737-1744.
[224]
Paisan-Ruiz, C.; Nath, P.; Washecka, N.; Gibbs, J.R.; Singleton, A.B. Comprehensive analysis of LRRK2 in publicly available Parkinson’s disease cases and neurologically normal controls. Hum. Mutat., 2008, 29, 485-490.
[225]
Clark, L.N.; Kisselev, S.; Park, N.; Ross, B.; Verbitsky, M.; Rios, E.; Alcalay, R.N.; Lee, J.H.; Louis, E.D. Mutations in the Parkinson’s disease genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA), are not associated with essential tremor. Parkinsonism Relat. Disord., 2010, 16, 132-135.
[226]
Greggio, E.; Cookson, M.R. Leucine-rich repeat kinase 2 mutations and Parkinson’s disease: Three questions. ASN Neuro, 2009, 1, e00002.
[227]
Schlitter, A.M.; Woitalla, D.; Mueller, T.; Epplen, J.T.; Dekomien, G. The LRRK2 gene in Parkinson’s disease: Mutation screening in patients from Germany. J. Neurol. Neurosurg. Psychiatry, 2006, 77, 891-892.
[228]
Wheway, G.; Schmidts, M.; Mans, D.A.; Szymanska, K.; Nguyen, T.T.; Racher, H.; Phelps, I.G.; Toedt, G.; Kennedy, J.; Wunderlich, K.A.; Sorusch, N.; Abdelhamed, Z.A.; Natarajan, S.; Herridge, W.; van Reeuwijk, J.; Horn, N.; Boldt, K.; Parry, D.A.; Letteboer, S.J.F.; Roosing, S.; Adams, M.; Bell, S.M.; Bond, J.; Higgins, J.; Morrison, E.E.; Tomlinson, D.C.; Slaats, G.G.; van Dam, T.J.P.; Huang, L.; Kessler, K.; Giessl, A.; Logan, C.V.; Boyle, E.A.; Shendure, J.; Anazi, S.; Aldahmesh, M.; Al Hazzaa, S.; Hegele, R.A.; Ober, C.; Frosk, P.; Mhanni, A.A.; Chodirker, B.N.; Chudley, A.E.; Lamont, R.; Bernier, F.P.; Beaulieu, C.L.; Gordon, P.; Pon, R.T.; Donahue, C.; Barkovich, A.J.; Wolf, L.; Toomes, C.; Thiel, C.T.; Boycott, K.M.; McKibbin, M.; Inglehearn, C.F. UK10K Consortium; University of Washington Center for Mendelian Genomics; Stewart, F.; Omran, H.; Huynen, M.A.; Sergouniotis, P.I.; Alkuraya, F.S.; Parboosingh, J.S.; Innes, A.M.; Willoughby, C.E.; Giles, R.H.; Webster, A.R.; Ueffing, M.; Blacque, O.; Gleeson, J.G.; Wolfrum, U.; Beales, P.L.; Gibson, T.; Doherty, D.; Mitchison, H.M.; Roepman, R.; Johnson, C.A. An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes. Nat. Cell Biol., 2015, 17, 1074-1087.
[229]
Wang, Z.; Iida, A.; Miyake, N.; Nishiguchi, K.M.; Fujita, K.; Nakazawa, T.; Alswaid, A.; Albalwi, M.A.; Kim, O.H.; Cho, T.J.; Lim, G.Y.; Isidor, B.; David, A.; Rustad, C.F.; Merckoll, E.; Westvik, J.; Stattin, E.L.; Grigelioniene, G.; Kou, I.; Nakajima, M.; Ohashi, H.; Smithson, S.; Matsumoto, N.; Nishimura, G.; Ikegawa, S. Axial spondylometaphyseal dysplasia is caused by C21orf2 mutations. PLoS One, 2016, 11, e0150555.
[230]
Suga, A.; Mizota, A.; Kato, M.; Kuniyoshi, K.; Yoshitake, K.; Sultan, W.; Yamazaki, M.; Shimomura, Y.; Ikeo, K.; Tsunoda, K.; Iwata, T. Identification of novel mutations in the LRR-Cap domain of C21orf2 in Japanese patients with retinitis pigmentosa and cone-rod dystrophy. Invest. Ophthalmol. Vis. Sci., 2016, 57, 4255-4263.
[231]
McInerney-Leo, A.M.; Wheeler, L.; Marshall, M.S.; Anderson, L.K.; Zankl, A.; Brown, M.A.; Leo, P.J.; Wicking, C.; Duncan, E.L. Homozygous variant in C21orf2 in a case of Jeune syndrome with severe thoracic involvement: Extending the phenotypic spectrum. Am. J. Med. Genet. A., 2017, 173, 1698-1704.
[232]
Khan, A.O.; Eisenberger, T.; Nagel-Wolfrum, K.; Wolfrum, U.; Bolz, H.J. C21orf2 is mutated in recessive early-onset retinal dystrophy with macular staphyloma and encodes a protein that localises to the photoreceptor primary cilium. Br. J. Ophthalmol., 2015, 99, 1725-1731.
[233]
Sferra, A.; Baillat, G.; Rizza, T.; Barresi, S.; Flex, E.; Tasca, G.; D’Amico, A.; Bellacchio, E.; Ciolfi, A.; Caputo, V.; Cecchetti, S.; Torella, A.; Zanni, G.; Diodato, D.; Piermarini, E.; Niceta, M.; Coppola, A.; Tedeschi, E.; Martinelli, D.; Dionisi-Vici, C.; Nigro, V.; Dallapiccola, B.; Compagnucci, C.; Tartaglia, M.; Haase, G.; Bertini, E. TBCE mutations cause early-onset progressive encephalopathy with distal spinal muscular atrophy. Am. J. Hum. Genet., 2016, 99, 974-983.
[234]
Klinkhamer, M.P.; Groen, N.A.; van der Zon, G.C.; Lindhout, D.; Sandkuyl, L.A.; Krans, H.M.; Moller, W.; Maassen, J.A. A leucine-to-proline mutation in the insulin receptor in a family with insulin resistance. EMBO J., 1989, •••, 2503-2507.
[235]
Kadowaki, T.; Kadowaki, H.; Accili, D.; Taylor, S.I. Substitution of lysine for asparagine at position 15 in the alpha-subunit of the human insulin receptor. A mutation that impairs transport of receptors to the cell surface and decreases the affinity of insulin binding. J. Biol. Chem., 1990, 265, 19143-19150.
[236]
Kadowaki, T.; Kadowaki, H.; Rechler, M.M.; Serrano-Rios, M.; Roth, J.; Gorden, P.; Taylor, S.I. Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance. J. Clin. Invest., 1990, 86, 254-264.
[237]
Barbetti, F.; Gejman, P.V.; Taylor, S.I.; Raben, N.; Cama, A.; Bonora, E.; Pizzo, P.; Moghetti, P.; Muggeo, M.; Roth, J. Detection of mutations in insulin receptor gene by denaturing gradient gel electrophoresis. Diabetes, 1992, 41, 408-415.
[238]
van der Vorm, E.R.; van der Zon, G.C.; Moller, W.; Krans, H.M.; Lindhout, D.; Maassen, J.A. An Arg for Gly substitution at position 31 in the insulin receptor, linked to insulin resistance, inhibits receptor processing and transport. J. Biol. Chem., 1992, 267, 66-71.
[239]
Carrera, P.; Cordera, R.; Ferrari, M.; Cremonesi, L.; Taramelli, R.; Andraghetti, G.; Carducci, C.; Dozio, N.; Pozza, G.; Taylor, S.I.; Mlcossl, P.; Barbettl, F. Substitution of Leu for Pro-193 in the insulin receptor in a patient with a genetic form of severe insulin resistance. Hum. Mol. Genet., 1993, 2, 1437-1441.
[240]
Lebrun, C.; Baron, V.; Kaliman, P.; Gautier, N.; Dolais-Kitabgi, J.; Taylor, S.; Accili, D.; Van Obberghen, E. Antibodies to the extracellular receptor domain restore the hormone-insensitive kinase and conformation of the mutant insulin receptor valine 382. J. Biol. Chem., 1993, 268, 11272-11277.
[241]
al-Gazali, L.I.; Khalil, M.; Devadas, K. A syndrome of insulin resistance resembling leprechaunism in five sibs of consanguineous parents. J. Med. Genet., 1993, 30, 470-475.
[242]
Longo, N.; Langley, S.D.; Griffin, L.D.; Elsas, L.J. Activation of glucose transport by a natural mutation in the human insulin receptor. Proc. Natl. Acad. Sci. USA, 1993, 90, 60-64.
[243]
Krook, A.; Kumar, S.; Laing, I.; Boulton, A.J.; Wass, J.A.; O’Rahilly, S. Molecular scanning of the insulin receptor gene in syndromes of insulin resistance. Diabetes, 1994, 43, 357-368.
[244]
van der Vorm, E.R.; Kuipers, A.; Kielkopf-Renner, S.; Krans, H.M.; Moller, W.; Maassen, J.A. A mutation in the insulin receptor that impairs proreceptor processing but not insulin binding. J. Biol. Chem., 1994, 269, 14297-14302.
[245]
Hone, J.; Accili, D.; al-Gazali, L.I.; Lestringant, G.; Orban, T.; Taylor, S.I. Homozygosity for a new mutation (Ile119-->Met) in the insulin receptor gene in five sibs with familial insulin resistance. J. Med. Genet., 1994, 31, 715-716.
[246]
Longo, N.; Langley, S.D.; Griffin, L.D.; Elsas, L.J. Two mutations in the insulin receptor gene of a patient with leprechaunism: Application to prenatal diagnosis. J. Clin. Endocrinol. Metab., 1995, 80, 1496-1501.
[247]
Desbois-Mouthon, C.; Sert-Langeron, C.; Magre, J.; Oreal, E.; Blivet, M.J.; Flori, E.; Besmond, C.; Capeau, J.; Caron, M. Deletion of Asn281 in the alpha-subunit of the human insulin receptor causes constitutive activation of the receptor and insulin desensitization. J. Clin. Endocrinol. Metab., 1996, 81, 719-727.
[248]
Rouard, M.; Macari, F.; Bouix, O.; Lautier, C.; Brun, J.F.; Lefebvre, P.; Renard, E.; Bringer, J.; Jaffiol, C.; Grigorescu, F. Identification of two novel insulin receptor mutations, Asp59Gly and Leu62Pro, in type A syndrome of extreme insulin resistance. Biochem. Biophys. Res. Commun., 1997, 234, 764-768.
[249]
Rique, S.; Nogues, C.; Ibanez, L.; Marcos, M.V.; Ferragut, J.; Carrascosa, A.; Potau, N. Identification of three novel mutations in the insulin receptor gene in type A insulin resistant patients. Clin. Genet., 2000, 57, 67-69.
[250]
Osawa, H.; Nishimiya, T.; Ochi, M.; Niiya, T.; Onuma, H.; Kitamuro, F.; Kaino, Y.; Kida, K.; Makino, H. Identification of novel C253Y missense and Y864X nonsense mutations in the insulin receptor gene in type A insulin-resistant patients. Clin. Genet., 2001, 59, 194-197.
[251]
Hamer, I.; Foti, M.; Emkey, R.; Cordier-Bussat, M.; Philippe, J.; De Meyts, P.; Maeder, C.; Kahn, C.R.; Carpentier, J.L. An arginine to cysteine(252) mutation in insulin receptors from a patient with severe insulin resistance inhibits receptor internalisation but preserves signalling events. Diabetologia, 2002, 45, 657-667.
[252]
Longo, N.; Wang, Y.; Smith, S.A.; Langley, S.D.; DiMeglio, L.A.; Giannella-Neto, D. Genotype-phenotype correlation in inherited severe insulin resistance. Hum. Mol. Genet., 2002, 11, 1465-1475.
[253]
George, S.; Johansen, A.; Soos, M.A.; Mortensen, H.; Gammeltoft, S.; Saudek, V.; Siddle, K.; Hansen, L.; O’Rahilly, S. Deletion of V335 from the L2 domain of the insulin receptor results in a conformationally abnormal receptor that is unable to bind insulin and causes Donohue’s syndrome in a human subject. Endocrinology, 2003, 144, 631-637.
[254]
Maassen, J.A.; Tobias, E.S.; Kayserilli, H.; Tukel, T.; Yuksel-Apak, M.; D’Haens, E.; Kleijer, W.J.; Fery, F.; van der Zon, G.C. Identification and functional assessment of novel and known insulin receptor mutations in five patients with syndromes of severe insulin resistance. J. Clin. Endocrinol. Metab., 2003, 88, 4251-4257.
[255]
Tuthill, A.; Semple, R.K.; Day, R.; Soos, M.A.; Sweeney, E.; Seymour, P.J.; Didi, M.; O’Rahilly, S. Functional characterization of a novel insulin receptor mutation contributing to Rabson-Mendenhall syndrome. Clin. Endocrinol. (Oxf.), 2007, 66, 21-26.
[256]
Accili, D.; Frapier, C.; Mosthaf, L.; McKeon, C.; Elbein, S.C.; Permutt, M.A.; Ramos, E.; Lander, E.; Ullrich, A.; Taylor, S.I. A mutation in the insulin receptor gene that impairs transport of the receptor to the plasma membrane and causes insulin-resistant diabetes. EMBO J., 1989, 8, 2509-2517.
[257]
Falik Zaccai, T.C.; Kalfon, L.; Klar, A.; Elisha, M.B.; Hurvitz, H.; Weingarten, G.; Chechik, E.; Fleisher Sheffer, V.; Haj Yahya, R.; Meidan, G.; Gross-Kieselstein, E.; Bauman, D.; Hershkovitz, S.; Yaron, Y.; Orr-Urtreger, A.; Wertheimer, E. Two novel mutations identified in familial cases with Donohue syndrome. Mol. Genet. Genomic Med., 2014, 2, 64-72.
[258]
Campbell, P.; Morton, P.E.; Takeichi, T.; Salam, A.; Roberts, N.; Proudfoot, L.E.; Mellerio, J.E.; Aminu, K.; Wellington, C.; Patil, S.N. Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR. J. Invest. Dermatol., 2014, 134, 2570-2578.
[259]
Miyashita, H.; Kretsinger, R.H.; Matsushima, N. Comparative structural analysis of the extracellular regions of the insulin and epidermal growth factor receptors whose L1 and L2 domains have non-canonical, leucinerich repeats. Enliven: Bioinformatics, 2014, 1, 1-9.
[260]
Wirehn, J.; Carlsson, K.; Herland, A.; Persson, E.; Carlsson, U.; Svensson, M.; Hammarstrom, P. Activity, folding, misfolding, and aggregation in vitro of the naturally occurring human tissue factor mutant R200W. Biochemistry, 2005, 44, 6755-6763.
[261]
Ohto, U.; Fukase, K.; Miyake, K.; Shimizu, T. Structural basis of species-specific endotoxin sensing by innate immune receptor TLR4/MD-2. Proc. Natl. Acad. Sci. USA, 2012, 109, 7421-7426.
[262]
Ayers, J.; Lelie, H.; Workman, A.; Prudencio, M.; Brown, H.; Fromholt, S.; Valentine, J.; Whitelegge, J.; Borchelt, D. Distinctive features of the D101N and D101G variants of superoxide dismutase 1; two mutations that produce rapidly progressing motor neuron disease. J. Neurochem., 2014, 128, 305-314.
[263]
Leonardi, E.; Andreazza, S.; Vanin, S.; Busolin, G.; Nobile, C.; Tosatto, S.C. A computational model of the LGI1 protein suggests a common binding site for ADAM proteins. PLoS One, 2011, 6, e18142.
[264]
David, A.; Kelley, L.A.; Sternberg, M.J. A new structural model of the acid-labile subunit: Pathogenetic mechanisms of short stature-causing mutations. J. Mol. Endocrinol., 2012, 49, 213-220.
[265]
Iyer, S.; Acharya, K.R.; Subramanian, V. Prediction of structural consequences for disease causing variants in C21orf2 protein using computational approaches. J. Biomol. Struct. Dyn., 2018, 7, 1-16.
[266]
He, X.L.; Bazan, J.F.; McDermott, G.; Park, J.B.; Wang, K.; Tessier-Lavigne, M.; He, Z.; Garcia, K.C. Structure of the Nogo receptor ectodomain: A recognition module implicated in myelin inhibition. Neuron, 2003, 38, 177-185.
[267]
Yamagata, A.; Miyazaki, Y.; Yokoi, N.; Shigematsu, H.; Sato, Y.; Goto-Ito, S.; Maeda, A.; Goto, T.; Sanbo, M.; Hirabayashi, M.; Shirouzu, M.; Fukata, Y.; Fukata, M. Fukai. S. Structural basis of epilepsy-related ligand-receptor complex LGI1-ADAM22. Nat. Commun., 2018, 9, 1546.
[268]
Smits, G.; Govaerts, C.; Nubourgh, I.; Pardo, L.; Vassart, G.; Costagliola, S. Lysine 183 and glutamic acid 157 of the TSH receptor: Two interacting residues with a key role in determining specificity toward TSH and human CG. Mol. Endocrinol., 2002, 16, 722-735.
[269]
Newton, C.L.; Anderson, R.C.; Katz, A.A.; Millar, R.P. Loss-of-function mutations in the human luteinizing hormone receptor predominantly cause intracellular retention. Endocrinology, 2016, 157, 4364-4377.
[270]
McEwan, P.A.; Yang, W.; Carr, K.H.; Mo, X.; Zheng, X.; Li, R.; Emsley, J. Quaternary organization of GPIb-IX complex and insights into Bernard-Soulier syndrome revealed by the structures of GPIbbeta and a GPIbbeta/GPIX chimera. Blood, 2011, 118, 5292-5301.
[271]
Scott, P.G.; McEwan, P.A.; Dodd, C.M.; Bergmann, E.M.; Bishop, P.N.; Bella, J. Crystal structure of the dimeric protein core of decorin, the archetypal small leucine-rich repeat proteoglycan. Proc. Natl. Acad. Sci. USA, 2004, 101, 5633-15638.
[272]
Paracuellos, P.; Kalamajski, S.; Bonnac, A.; Bihanc, D.; Richard, W.; Farndale, R.W.; Hohenestera, E. Structural and functional analysis of two small leucine-rich repeat proteoglycans, fibromodulin and chondroadherin. Matrix Biol., 2017, 63, 106-116.
[273]
Pronker, M.F.; Tas, R.P.; Vlieg, H.C.; Janssen, B.J.C. Nogo Receptor crystal structures with a native disulfide pattern suggest a novelmode of self-interaction. Acta Crystallogr. D Struct. Biol., 2017, 73, 860-876.
[274]
Jiang, X.; Liu, H.; Chen, X.; Chen, P.H.; Fischer, D.; Sriraman, V.; Yu, H.N.; Arkinstall, S.; He, X. Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor. Proc. Natl. Acad. Sci. USA, 2012, 109, 12491-12496.
[275]
Ho, S.C.; Van Sande, J.; Lefort, A.; Vassart, G.; Costagliola, S. Effects of mutations involving the highly conserved S281HCC motif in the extracellular domain of the thyrotropin (TSH) receptor on TSH binding and constitutive activity. Endocrinology, 2001, 142, 2760-2767.
[276]
Blenner, M.A.; Dong, X.; Springer, T.A. Structural basis of regulation of von Willebrand factor binding to glycoprotein Ib. J. Biol. Chem., 2014, 289, 5565-5579.
[277]
Sparrow, L.G.; McKern, N.M.; Gorman, J.J.; Strike, P.M.; Robinson, C.P.; Bentley, J.D.; Ward, C.W. The disulfide bonds in the C-terminal domains of the human insulin receptor ectodomain. J. Biol. Chem., 1997, 272, 29460-29467.
[278]
Dao, T.P.; Majumdar, A.; Barrick, D. Capping motifs stabilize the leucine-rich repeat protein PP32 and rigidify adjacent repeats. Protein Sci., 2014, 23, 801-811.
[279]
Zhang, Y.; Berghaus, M.; Klein, S.; Jenkins, K.; Zhang, S.; McCallum, S.A.; Morgan, J.E.; Winter, R.; Barrick, D.; Royer, C.A. High-pressure NMR and SAXS reveals how capping modulates folding cooperativity of the pp32 leucine-rich repeat protein. J. Mol. Biol., 2018, 430, 1336-1349.
[280]
Vieux, E.F.; Barrick, D. Deletion of internal structured repeats increases the stability of a leucine-rich repeat protein, YopM. Biophys. Chem., 2011, 159, 152-161.
[281]
Courtemanche, N.; Barrick, D. Folding thermodynamics and kinetics of the leucine-rich repeat domain of the virulence factor Internalin B. Protein Sci., 2008, 17, 43-53.
[282]
Courtemanche, N.; Barrick, D. The leucine-rich repeat domain of Internalin B folds along a polarized N-terminal pathway. Structure, 2008, 16, 705-714.
[283]
Kloss, E.; Barrick, D. Thermodynamics, kinetics, and salt dependence of folding of YopM, a large leucine-rich repeat protein. J. Mol. Biol., 2008, 383, 1195-1209.
[284]
Freiberg, A.; Machner, M.P.; Pfeil, W.; Schubert, W.D.; Heinz, D.W.; Seckler, R. Folding and stability of the leucine-rich repeat domain of internalin B from Listeri monocytogenes. J. Mol. Biol., 2004, 337, 453-461.
[285]
Atkinson, J.; Martin, R. Mutations to nonsense codons in human genetic disease: implications for gene therapy by nonsense suppressor tRNAs. Nucleic Acids Res., 1994, 22, 1327-1334.
[286]
Sauna, Z.E.; Kimchi-Sarfaty, C. Understanding the contribution of synonymous mutations to human disease. Nat. Rev. Genet., 2011, 12, 683.
[287]
Gregg, R.G.; Kamermans, M.; Klooster, J.; Lukasiewicz, P.D.; Peachey, N.S.; Vessey, K.A.; McCall, M.A. Nyctalopin expression in retinal bipolar cells restores visual function in a mouse model of complete X-linked congenital stationary night blindness. J. Neurophysiol., 2007, 98, 3023-3033.
[288]
Pearring, J.N.; Bojang, P., Jr; Shen, Y.; Koike, C.; Furukawa, T.; Nawy, S.; Gregg, R.G. A role for nyctalopin, a small leucine-rich repeat protein, in localizing the TRP melastatin 1 channel to retinal depolarizing bipolar cell dendrites. J. Neurosci., 2011, 31, 10060-10066.
[289]
UniProtKB/Swiss-Prot.
[290]
Fan, Q.R.; Hendrickson, W.A. Structure of human follicle-stimulating hormone in complex with its receptor. Nature, 2005, 433, 269-277.
[291]
Seiradake, E.; del Toro, D.; Nagel, D.; Cop, F.; Hartl, R.; Ruff, T.; Seyit-Bremer, G.; Harlos, K.; Border, E.C.; Acker-Palmer, A.; Jones, E.Y.; Klein, R. FLRT structure: balancing repulsion and cell adhesion in cortical and vascular development. Neuron, 2014, 84, 370-385.
[292]
Lu, Y.C.; Nazarko, O.V.; Sando, R., III; Salzman, G.S.; Li, N.S.; Sudhof, T.C.; Arac, D. Structurtrophilin-FLRT-UNC5 interaction in cell adhesion. Structure, 2015, 23, 1678-1691.
[293]
Ranaivoson, F.M.; Liu, Q.; Martini, F.; Bergami, F.; von Daake, S.; Li, S.; Lee, D.; Demeler, B.; Hendrickson, W.A.; Comoletti, D. Structural and mechanistic insights into the latrophilin3-FLRT3 Complex that mediates glutamatergic synapse development. Structure, 2015, 23, 1665-1677.
[294]
O’Sullivan, M.L.; de Wit, J.; Savas, J.N.; Comoletti, D.; Otto-Hitt, S.; Yates, J.R., III; Ghosh, A. FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse development. Neuron, 2012, 73, 903-910.
[295]
Huizinga, E.G.; Tsuji, S.; Romijn, R.A.; Schiphorst, M.E.; de Groot, P.G.; Sixma, J.J.; Gros, P. Structures of glycoprotein Ibalpha and its complex with von Willebrand factor A1 domain. Science, 2002, 297, 1176-1179.
[296]
Dumas, J.J.; Kumar, R.; McDonagh, T.; Sullivan, F.; Stahl, M.L.; Somers, W.S.; Mosyak, L. Crystal structure of the wild-type von Willebrand factor A1-glycoprotein Ibalpha complex reveals conformation differences with a complex bearing von Willebrand disease mutations. J. Biol. Chem., 2004, 279, 23327-23334.
[297]
Um, J.W.; Kim, K.H.; Park, B.S.; Choi, Y.; Kim, D.; Kim, C.Y.; Kim, S.J.; Kim, M.; Ko, J.S.; Lee, S.G.; Choii, G.; Nam, J.; Heo, W.D.; Kim, E.; Lee, J.O.; Ko, J.; Kim, H.M. Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion. Nat. Commun., 2014, 5, 5423.
[298]
Zhang, L.; Chen, S.; Ruan, J.; Wu, J.; Tong, A.B.; Yin, Q.; Li, Y.; David, L.; Lu, A.; Wang, W.L.; Marks, C.; Ouyang, Q.; Zhang, X.; Mao, Y.; Wu, H. Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization. Science, 2015, 350, 404-409.
[299]
Diebolder, C.A.; Halff, E.F.; Koster, A.J.; Huizinga, E.G.; Koning, R.I. Cryoelectron tomography of the NAIP5/NLRC4 inflammasome: Implications for NLR activation. Structure, 2015, 23, 2349-2357.
[300]
Tenthorey, J.L.; Haloupek, N.; López-Blanco, J.R.; Grob, P.; Adamson, E.; Hartenian, E.; Lind, N.A.; Bourgeois, N.M.; Chacón, P.; Nogales, E.; Vance, R.E. The structural basis of flagellin detection by NAIP5: A strategy to limit pathogen immune evasion. Science, 2017, 358, 888-893.
[301]
Lanza, F. Bernard-Soulier syndrome (hemorrhagiparous thrombocytic dystrophy). Orphanet J. Rare Dis., 2006, 1, 46.
[302]
Berndt, M.C.; Andrews, R.K. Bernard-Soulier syndrome. Haematologica, 2011, 96, 355-359.
[303]
Ramasamy, I. Inherited bleeding disorders: Disorders of platelet adhesion and aggregation. Crit. Rev. Oncol. Hematol., 2004, 49, 1-35.
[304]
Duprez, L.; Parma, J.; Costagliola, S.; Hermans, J.; Van Sande, J.; Dumont, J.E.; Vassart, G. Constitutive activation of the TSH receptor by spontaneous mutations affecting the N-terminal extracellular domain. FEBS Lett., 1997, 409, 469-474.
[305]
Hebrant, A.; van Staveren, W.C.; Maenhaut, C.; Dumont, J.E. Leclere, J. Genetic hyperthyroidism: Hyperthyroidism due to activating TSHR mutations. Eur. J. Endocrinol., 2011, 164, 1-9.

© 2024 Bentham Science Publishers | Privacy Policy