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Title
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Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients
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Author
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Institution/Organisation
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Belgian Neurology Consortium
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Abstract
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| Mutation screening and phenotypic profiling of 2 amyotrophic lateral sclerosis(ALS) and frontotemporal dementia(FTD) associated genes, CHCHD10 and TUBA4A, were performed in a Belgian cohort of 459 FTD, 28 FTD-ALS, and 429 ALS patients. In CHCHD10, we identified a novel nonsense mutation (p.Gln108*) in a patient with atypical clinical FTD and pathology-confirmed Parkinson's disease (1/459, 0.22%) leading to loss of transcript. We further observed 3 previously described missense variants (p.Pro34Ser, p.Pro80Leu, and p.Pro96Thr) that were also present in the matched control series. In TUBA4A, we detected a novel frameshift mutation (p.Arg64Glyfs*90) leading to a truncated protein in 1 FTD patient (1/459 of 0.22%) with family history of Parkinson's disease and cognitive impairment, and a novel missense mutation (p.Thr381Met) in 2 sibs with familial ALS and memory problems (1 index patient/429, 0.23%) in whom we previously identified a pathogenic Chromosome 9 open reading frame 72 repeat expansion mutation. The present study confirms the role of CHCHD10 and TUBA4A in the FTD-ALS spectrum, although genetic variations in these 2 genes are extremely rare in the Belgian population and often associated with symptomatology of related neurodegenerative diseases including Parkinson's disease and Alzheimer's disease. |
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Language
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English
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Source (journal)
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Neurobiology of aging. - Fayetteville, N.Y.
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Publication
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Fayetteville, N.Y.
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2017
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ISSN
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0197-4580
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DOI
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10.1016/J.NEUROBIOLAGING.2016.12.008
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Volume/pages
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51
(2017)
, 8 p.
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Article Reference
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177.e9
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ISI
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000397168600020
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Pubmed ID
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28069311
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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Full text (publisher's version - intranet only)
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