Login Register Cart 0
Generic placeholder image

Cardiovascular & Hematological Disorders-Drug Targets

Editor-in-Chief

ISSN (Print): 1871-529X
ISSN (Online): 2212-4063

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Case Report

Factor X Deficiency Due to a Compound Heterozygosis Between a New Mutation (Gla72Asp) in Exon 2 and an Already Known one (Gly154Arg) in Exon 5: Factor X Mar Del Plata1)

Author(s): Antonio Girolami*, Diana Noemi Garcia de Paoletti, Marcelo Leonardo Nenkies, Silvia Ferrari and Hugo Guglielmone

Volume 19, Issue 2, 2019

Page: [169 - 173] Pages: 5

DOI: 10.2174/1871529X19666181212103944

Price: $65

Abstract

Background: Investigation of rare bleeding disorders in Latin-America.

Objectives: The report of a new case of FX deficiency due to a compound heterozygosis.

Methods: Accepted clotting procedures were used. Sequencing of DNA was carried out by means of Applied Biosystems Instruments.

Results: A compound heterozygote due to the association of a new mutation (Gla72Asp) with an already known mutation (Gly154Arg) of the FX gene is reported. The proposita is a 38 year old female who had a moderate bleeding tendency (menorrhagia, epistaxis, easy bruising). The proposita has never received substitution therapy but in the occasion of a uterine biopsy. The mother was asymptomatic but was a heterozygote for the new mutation. The father was asymptomatic but had deserted the family and could not be investigated. After this abandonment the mother of the proposita re-married with an asymptomatic man and she gave birth to a son who was asymptomatic but was also heterozygous for the new mutation (Gla72Asp). As a consequence it has to be assumed that the first husband of the mother of the proposita was heterozygous for the known mutation (Gly154Arg).

Conclusions: This is the third case of a new mutation in the FX gene reported, during the past few years, in Argentina.

Keywords: Factor X, deficiency, compound heterozygosis, bleeding, menorrhagia.

« Previous Next »
Graphical Abstract

[1]
Quick, A.J. Congenital hypoprothrombinemia and pseudo-hypoprothrombinemia. Lancet, 1947, 2, 379-382.
[2]
Graham, J.B.; Barrow, E.M.; Hougie, C. Stuart clotting defect. II. Genetic aspects of a new hemorrhagic state. J. Clin. Invest., 1957, 36, 497-503.
[3]
Hougie, C.; Barrow, E.M.; Graham, J.B. Stuart clotting defect I. segregation of an hereditary hemorrhagic state from the heterogeneous group heretofore called stable factor (SPCA, Proconvertin, Factor VII) deficiency. J. Clin. Invest., 1957, 36, 485-496.
[4]
Telfer, T.P.; Denson, K.W.; Wright, D.R. A new coagulation defect. Br. J. Haematol., 1956, 2, 308-316.
[5]
Alexander, B.; Goldstein, R.; Landwehr, G.; Cook, C.D.; Addelson, E.; Wilson, C. Congenital spca deficiency: a hitherto unrecognized coagulation defect with hemorrhage rectified by serum and serum fractions. J. Clin. Invest., 1951, 30, 596-608.
[6]
Duckert, F.; Jung, E.; Shmerling, D.H. A hitherto undescribed congenital haemorrhagic diathesis probably due to fibrin stabilizing factor deficiency. Thromb. Diath. Haemorrh., 1960, 5, 179-186.
[7]
Bachmann, F.; Duckert, F.; Flückiger, P.; Hitzig, W.; Koller, F. Uber einen neuartigen kongenitalen gerinnungs defect (Mangel an Stuart Faktor). Thromb. Diath. Haemorrh., 1957, 1, 87-92.
[8]
Herrmann, F.H.; Auerswald, G.; Ruiz-Saez, A.; Navarrete, M.; Pollmann, H.; Lopaciuk, S.; Batorova, A.; Wulff, K. Greifswald Factor X Deficiency Study Group. Factor X deficiency: clinical manifestation of 102 subjects from Europe and Latin America with mutations in the factor 10 gene. Haemophilia, 2006, 12, 479-489.
[9]
Girolami, A.; Molina, M.A.; Galletti, M.L.; Ferrari, S.; Sambado, L.; Guglielmone, H. A family with factor X deficiency from Argentina: a compound heterozygosis because of the combination of a new mutation (Gln138Arg) with an already known one (Glu350Lys). Blood Coagul. Fibrinolysis, 2016, 27, 732-736.
[10]
Girolami, A.; Minoldo, S.; Ferrari, S.; Colussi, D.; Lombardi, A.M.; Guglielmone, H. Congenital FX deficiency rio tercero: a new heterozygous missense mutation (Cys241Gly) with a potentiating effect by a polymorphism (c. 503-57C>T). Cardiovasc. Hematol. Disord. Drug Targets, 2017, 17, 136-141.
[11]
Uprichard, J.; Perry, D.J. Factor X deficiency. Blood Rev., 2002, 16, 97-110.
[12]
Herrmann, F.H.; Wulff, K.; Auerswald, G.; Schulman, S.; Astermark, J.; Batorova, A.; Kreuz, W.; Pollmann, H.; Ruiz-Saez, A.; De Bosch, N.; Salazar-Sanchez, L. Factor VII deficiency: clinical manifestation of 717 subjects from Europe and Latin America with mutations in the factor 7 gene. Haemophilia, 2009, 15, 267-280.
[13]
Lefkowitz, J.B.; Weller, A.; Nuss, R.; Santiago-Borrero, P.J.; Brown, D.L.; Ortiz, I.R. A common mutation, Arg457->Gln, links prothrombin deficiencies in the Puerto Rican population. J. Thromb. Haemost., 2003, 1, 2381-2388.
[14]
Wallmark, A.; Ho, C.; Monroroe, D.; Tenglom, L.; High, K. Molecular defect in FX Okero, a mild congenital FX deficiency. Thromb. Haemost., 1991, 65, 1263.
[15]
Morishita, E.; Yamaguchi, K.; Asakura, H.; Saito, M.; Yamazaki, M.; Ontachi, Y.; Mizutani, T.; Kato, M.; Nakao, S. One missense mutation in the factor X gene causing factor X deficiency-factor x kanazawa. Internet J. Hematol., 2001, 73, 390-392.
[16]
Girolami, A.; Molaro, G.; Lazzarin, M.; Scarpa, R.; Brunetti, A.A. “new” congenital haemorrhagic condition due to the presence of an abnormal factor X (factor X Friuli): study of a large kindred. Br. J. Haematol., 1970, 19, 179-192.
[17]
Sanger, F.; Nicklen, S.; Coulson, A.R. DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA, 1977, 74, 5463-5467.
[18]
Perry, D.J. Factor VII deficiency. Br. J. Haematol., 2002, 118, 689-700.
[19]
Girolami, A.; Allemand, E.; Scandellari, R.; Lombardi, A.M.; Girolami, B. The clinical and laboratory significance of cases of congenital FX deficiency due to defects in the Gla-domain. Hematology, 2009, 14, 177-1181.
[20]
Zama, T.; Murata, M.; Watanabe, R.; Yokoyama, K.; Moriki, T.; Ambo, H.; Murakami, H.; Kikuchi, M.; Ikeda, Y. A family with hereditary factor X deficiency with a point mutation Gla32 to Gln in the Gla domain (factor X Tokyo). Br. J. Haematol., 1999, 106, 809-811.
[21]
Girolami, A.; Scarparo, P. SCandellari, R.; Allemand, E. Congenital FX deficiency with a defect only on predominant in the extrinsic or the intrinsic system: a crtitical evaluation. Am. J. Hematol., 2008, 83, 668-671.
[22]
Girolami, A.; Scapin, M.; Scarparo, P.; Vettore, S. Different genotypes are responsible for the normal Russel Viper Venoum assays seen in some cases of FX deficiency. Am. J. Hematol., 2008, 83, 884-885.
[23]
Watzke, H.H.; Walimark, A.; Hamaguchi, N.; Giardina, P.; Stafford, D.W.; High, K.A.; Factor, X. Santo Domingo. J. Clin. Invest., 1991, 88, 1685-1689.
[24]
Jayandharan, G.; Viswabandya, A.; Baidya, S.; Nair, S.C.
Shaji, R.V.; George, B.; Chandy, M.; Srivastava, A. Six novel mutations including triple heterozygosity for Phe31Ser, 514delT and 516T->G factor X gene mutations are responsible for congenital factor X deficiency in patients of Nepali and Indian origin. J. Thromb. Haemost., 2005, 3, 1482-1487.
[25]
Au, W.Y.; Lam, C.C.; Cheung, W.C.; Kwong, Y.L. Two novel factor X gene mutations in a Chinese family with factor X deficiency. Ann. Hematol., 2004, 83, 304-306.
[26]
Ijima, K.; Murakami, M.; Kimura, O.; Murakami, F.; Shimomura, T.; Ikawa, S. A dysfunctional factor X (factor X kurayoshi) with a substitution of Arg139 for Ser at the carboxyl-terminus of the light chain. Thromb. Res., 2001, 101, 311-316.
[27]
Mota, L.; Shetty, S.; Idicula-Thomas, S.; Ghosh, K. Molecular basis of factor X deficiency cases from India. Haemophilia, 2010, 16, 693-697.
[28]
Liang, Q.; Chen, Q.; Ding, Q.; Wu, F.; Wang, X.; Xi, X.; Wang, H. Six novel missense mutations causing factor X deficiency and application of thrombin generation test. Thromb. Res., 2013, 131, 554-559.
[29]
Dorgalaleh, A.; Zaker, F.; Tabibian, S.; Alizadeh, S.; Dorgalele, S.; Hosseini, S.; Shamsizadeh, M. Spectrum of factor X gene mutations in Iranian patients with congenital factor X deficiency. Blood Coagul. Fibrinolysis, 2016, 27, 324-327.
[30]
Smoom, R.; Abushkedim, I.; Darwish, H. Identification of two Novel Mutations in the Factor X Gene; A 5′ Donor Splice-Site Mutation (IVS1+1G?T) and a missense Mutation (Asp413Asn G>T) in Unrelated Palestinian Factor X Deficient Patients. J. Blood Disord. Transfus., 2015, 6, 4.

Rights & Permissions Print Cite
Article Metrics
61
6
World Hemophilia Day
© 2024 Bentham Science Publishers | Privacy Policy