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. © 2014 American Academy of Neurology.

Picard, F., Makrythanasis, P., Navarro, V., Ishida, S., de Bellescize, J., Ville, D., et al. (2014). DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy. NEUROLOGY, 82, 2101-2106 [10.1212/WNL.0000000000000488].

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

COMBI, ROMINA;
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 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. © 2014 American Academy of Neurology.
Articolo in rivista - Articolo scientifico
ADNFLE, FFEVF, nicotinic receptor, focal epilepsies, autosomal dominant, mTOR
English
10-giu-2014
82
2101
2106
none
Picard, F., Makrythanasis, P., Navarro, V., Ishida, S., de Bellescize, J., Ville, D., et al. (2014). DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy. NEUROLOGY, 82, 2101-2106 [10.1212/WNL.0000000000000488].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/51556
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