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Title
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DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy
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Author
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Abstract
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| Objective: To study the prevalence of DEPDC5 mutations in a series of 30 small European families with a phenotype compatible with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Methods: Thirty unrelated families referred with ADNFLE were recruited in France, Italy, Germany, Belgium, and Norway. Whole-exome sequencing was performed in 10 probands and direct sequencing of the DEPDC5 coding sequence in 20 probands. Testing for nonsense-mediated messenger RNA decay (NMD) was performed in lymphoblastic cells. Results: Exome sequencing revealed a splice acceptor mutation (c.2355-2A>G) in DEPDC5 in the proband of aGerman family. In addition, 3 nonsense DEPDC5 mutations (p.Arg487*, p.Arg1087*, and p.Trp1369*) were detected in the probands of 2 French and one Belgian family. The nonsense mutations p.Arg487* and p.Arg1087* were targeted by NMD, leading to the degradation of the mutated transcripts. At the clinical level, 78% of the patients with DEPDC5 mutations were drug resistant. Conclusions: DEPDC5 loss-of-function mutations were found in 13% of the families with a presentation of ADNFLE. The rate of drug resistance was high in patients with DEPDC5 mutations. Small ADNFLE pedigrees with DEPDC5 mutations might actually represent a part of the broader familial focal epilepsy with variable foci phenotype. |
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Language
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English
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Source (journal)
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Neurology / American Academy of Neurology. - Minneapolis, Minn
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Publication
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Minneapolis, Minn
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2014
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ISSN
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0028-3878
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DOI
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10.1212/WNL.0000000000000488
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Volume/pages
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82
:23
(2014)
, p. 2101-2106
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ISI
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000342819500013
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Pubmed ID
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24814846
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Full text (Publisher's DOI)
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