DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy - PubMed (original) (raw)

. 2014 Jun 10;82(23):2101-6.

doi: 10.1212/WNL.0000000000000488. Epub 2014 May 9.

Periklis Makrythanasis 1, Vincent Navarro 1, Saeko Ishida 1, Julitta de Bellescize 1, Dorothée Ville 1, Sarah Weckhuysen 1, Erwin Fosselle 1, Arvid Suls 1, Peter De Jonghe 1, Maryline Vasselon Raina 1, Gaetan Lesca 1, Christel Depienne 1, Isabelle An-Gourfinkel 1, Mihaela Vlaicu 1, Michel Baulac 1, Emeline Mundwiller 1, Philippe Couarch 1, Romina Combi 1, Luigi Ferini-Strambi 1, Antonio Gambardella 1, Stylianos E Antonarakis 1, Eric Leguern 1, Ortrud Steinlein 1, Stéphanie Baulac 1

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DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy

Fabienne Picard et al. Neurology. 2014.

Abstract

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 a German 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.

© 2014 American Academy of Neurology.

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