Abstract
Frontotemporal Lobar Degeneration (FTLD) is a genetically and pathologically heterogeneous disorder characterized by behavioral change, executive dysfunction and language impairment associated with frontal and temporal lobe degeneration. Three major clinical subtypes have been identified so far, namely behaviour variant Frontotemporal dementia (bvFTD), Semantic Dementia (SD) and Progressive Non-Fluent Aphasia (PNFA). FTLD might also overlap with atypical parkinsonisms or motor neuron disease. Several pathogenetic mutations have been associated with specific pathological and clinical correlates. FTLD associated with either Microtuble Associated Protein Tau (MAPT) or Progranulin (PGRN) mutations is recognised as the most common form of autosomal dominant inherited disorder. However, monogenic mutations account for only about one third of all FTLD cases. Several studies have evaluated the contribution of genetic background in non-monogenic forms of FTLD, with the attempt to establish its role in increasing disease risk and in modulating clinical phenotypes. Specific MAPT and PGRN polymorphisms have been demonstrated to affect disease onset, clinical features and prognosis of FTLD, and genetic variations within other genes appear to play a role in influencing disease risk and clinical expression of FTLD.
The aim of the present review is to discuss the impact and the role of genetic background in non-monogenic forms of FTLD, to highlight new potential pathogenetic and therapeutic targets.
Keywords: Frontotemporal lobar degeneration, frontotemporal dementia, genetics, polymorphism, risk factors, FTLD, MAPT, PGRN, Microtuble Associated Protein Tau, parkinsonisms, non-monogenic
Mini-Reviews in Medicinal Chemistry
Title: Genetic Contributors to Frontotemporal Lobar Degeneration: Beyond Monogenic Disease
Volume: 11 Issue: 11
Author(s): B. Borroni, A. Pilotto, M. Bianchi, N. Gilberti and A. Padovani
Affiliation:
Keywords: Frontotemporal lobar degeneration, frontotemporal dementia, genetics, polymorphism, risk factors, FTLD, MAPT, PGRN, Microtuble Associated Protein Tau, parkinsonisms, non-monogenic
Abstract: Frontotemporal Lobar Degeneration (FTLD) is a genetically and pathologically heterogeneous disorder characterized by behavioral change, executive dysfunction and language impairment associated with frontal and temporal lobe degeneration. Three major clinical subtypes have been identified so far, namely behaviour variant Frontotemporal dementia (bvFTD), Semantic Dementia (SD) and Progressive Non-Fluent Aphasia (PNFA). FTLD might also overlap with atypical parkinsonisms or motor neuron disease. Several pathogenetic mutations have been associated with specific pathological and clinical correlates. FTLD associated with either Microtuble Associated Protein Tau (MAPT) or Progranulin (PGRN) mutations is recognised as the most common form of autosomal dominant inherited disorder. However, monogenic mutations account for only about one third of all FTLD cases. Several studies have evaluated the contribution of genetic background in non-monogenic forms of FTLD, with the attempt to establish its role in increasing disease risk and in modulating clinical phenotypes. Specific MAPT and PGRN polymorphisms have been demonstrated to affect disease onset, clinical features and prognosis of FTLD, and genetic variations within other genes appear to play a role in influencing disease risk and clinical expression of FTLD.
The aim of the present review is to discuss the impact and the role of genetic background in non-monogenic forms of FTLD, to highlight new potential pathogenetic and therapeutic targets.
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Borroni B., Pilotto A., Bianchi M., Gilberti N. and Padovani A., Genetic Contributors to Frontotemporal Lobar Degeneration: Beyond Monogenic Disease, Mini-Reviews in Medicinal Chemistry 2011; 11 (11) . https://dx.doi.org/10.2174/138955711797068517
DOI https://dx.doi.org/10.2174/138955711797068517 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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