DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy
- PMID: 24814846
- DOI: 10.1212/WNL.0000000000000488
DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy
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.
Similar articles
-
Familial focal epilepsy with focal cortical dysplasia due to DEPDC5 mutations.Ann Neurol. 2015 Apr;77(4):675-83. doi: 10.1002/ana.24368. Epub 2015 Mar 13. Ann Neurol. 2015. PMID: 25623524
-
DEPDC5 mutations are not a frequent cause of familial temporal lobe epilepsy.Epilepsia. 2015 Oct;56(10):e168-71. doi: 10.1111/epi.13094. Epub 2015 Jul 27. Epilepsia. 2015. PMID: 26216793
-
Genetics advances in autosomal dominant focal epilepsies: focus on DEPDC5.Prog Brain Res. 2014;213:123-39. doi: 10.1016/B978-0-444-63326-2.00007-7. Prog Brain Res. 2014. PMID: 25194487 Review.
-
Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations.Ann Neurol. 2014 May;75(5):782-7. doi: 10.1002/ana.24126. Epub 2014 Apr 14. Ann Neurol. 2014. PMID: 24585383
-
Genetic heterogeneity in familial nocturnal frontal lobe epilepsy.Prog Brain Res. 2014;213:1-15. doi: 10.1016/B978-0-444-63326-2.00001-6. Prog Brain Res. 2014. PMID: 25194481 Review.
Cited by
-
Epileptic spasms are a feature of DEPDC5 mTORopathy.Neurol Genet. 2015 Jul 23;1(2):e17. doi: 10.1212/NXG.0000000000000016. eCollection 2015 Aug. Neurol Genet. 2015. PMID: 27066554 Free PMC article.
-
Molecular Genetics of Epilepsy: A Clinician's Perspective.Ann Indian Acad Neurol. 2017 Apr-Jun;20(2):96-102. doi: 10.4103/aian.AIAN_447_16. Ann Indian Acad Neurol. 2017. PMID: 28615892 Free PMC article. Review.
-
The genetics of the epilepsies.Curr Neurol Neurosci Rep. 2015 Jul;15(7):39. doi: 10.1007/s11910-015-0559-8. Curr Neurol Neurosci Rep. 2015. PMID: 26008807 Review.
-
GATOR1 Mutations Impair PI3 Kinase-Dependent Growth Factor Signaling Regulation of mTORC1.Int J Mol Sci. 2024 Feb 8;25(4):2068. doi: 10.3390/ijms25042068. Int J Mol Sci. 2024. PMID: 38396745 Free PMC article.
-
Sleep-Related Hypermotor Epilepsy: Etiology, Electro-Clinical Features, and Therapeutic Strategies.Nat Sci Sleep. 2021 Nov 13;13:2065-2084. doi: 10.2147/NSS.S330986. eCollection 2021. Nat Sci Sleep. 2021. PMID: 34803415 Free PMC article. Review.
Publication types
MeSH terms
Substances
Supplementary concepts
LinkOut - more resources
Full Text Sources
Other Literature Sources