Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients

Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Federica Perrone, Hung Phuoc Nguyen, Sara Van Mossevelde, Matthieu Moisse, Anne Sieben, Patrick Santens, Jan De Bleecker, Mathieu Vandenbulcke, Sebastiaan Engelborghs, Jonathan Baets, Patrick Cras, Rik Vandenberghe, Peter De Jonghe, Peter P. De Deyn, Jean-Jacques Martin, Philip Van Damme, Christine Van Broeckhoven, Julie van der Zee
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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