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A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the French‐Canadian population
Author(s) -
Martin C.,
Meloche C.,
Rioux M.F.,
Nguyen D.K.,
Carmant L.,
Andermann E.,
Gravel M.,
Cossette P.
Publication year - 2014
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12311
Subject(s) - epilepsy , mutation , genotyping , population , genetics , epilepsy syndromes , allele , biology , bioinformatics , medicine , gene , neuroscience , genotype , environmental health
Familial focal epilepsy with variable foci ( FFEVF ) is a heterogeneous epilepsy syndrome originally described in the French‐Canadian ( FC ) population. Mutations in DEPDC5 have recently been identified in multiple cases of FFEVF as well as in a wide spectrum of other familial focal epilepsies. In this study, we aimed to determine the frequency of mutation of this gene in our large cohort of FC individuals with FFEVF , as well as familial and sporadic cases with focal epilepsy. We report a recurrent p. R843X protein‐truncating mutation segregating in one large FFEVF and two small focal epilepsy FC families. Fine genotyping suggests an ancestral allele. A new p. T864M variant, predicted to be disease‐causing, was also identified in a small FC family. Overall, we identified DEPDC5 mutations in 5% of our familial and sporadic focal epilepsy cases (4/79). Our results support the view that mutations in the DEPDC5 gene are an important cause of autosomal dominant focal epilepsies in the FC population, including a founder mutation that is specific to this population. These findings may facilitate molecular diagnosis in clinical practice.

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