Epileptic spasms are a feature ofDEPDC5mTORopathy
Autor: | Samuel F. Berkovic, Simone Mandelstam, Douglas E. Crompton, Matthew Zemel, Gemma L. Carvill, Amy L Schneider, Jacinta M McMahon, A. Simon Harvey, Julia Saykally, Joseph Sullivan, Brigid M. Regan, Saul A. Mullen, Katherine B. Howell, Leanne M. Dibbens, Heather C Mefford, Ingrid E. Scheffer, Richard J. Leventer |
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Přispěvatelé: | Carvill, GL, Crompton, DE, Regan, BM, McMahon, JM, Saykally, J, Zemel, M, Schneider, AL, Dibbens, L, Howell, KB, Mandelstam, S, Leventer, RJ, Harvey, AS, Mullen, SA, Berkovic, SF, Sullivan, J, Scheffer, IE, Mefford, HC |
Rok vydání: | 2015 |
Předmět: |
familial focal epilepsy
epileptic spasms Bioinformatics DEPDC5 mutations Article 03 medical and health sciences Epilepsy spasms 0302 clinical medicine medicine Family history Genetics (clinical) 030304 developmental biology 0303 health sciences business.industry Cortical dysplasia medicine.disease NPRL3 DEPDC5 3. Good health Epileptic spasms Clinical research Cohort epilepsy Neurology (clinical) business 030217 neurology & neurosurgery |
Zdroj: | Neurology: Genetics |
ISSN: | 2376-7839 |
Popis: | usc Refereed/Peer-reviewed Objective: To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms. Methods: We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants. Results: We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms. We also describe 3 additional patients with DEPDC5 alterations and epileptic spasms: 2 from a previously described family and a third ascertained by clinical testing. Overall, we describe 6 patients from 5 families with spasms and DEPDC5 variants; 2 arose de novo and 3 were familial. Two individuals had focal cortical dysplasia. Clinical outcome was highly variable. Conclusions: While recent molecular findings in epileptic spasms emphasize the contribution of de novo mutations, we highlight the relevance of inherited mutations in the setting of a family history of focal epilepsies. We also illustrate the utility of clinical diagnostic testing and detailed phenotypic evaluation in characterizing the constellation of phenotypes associated with DEPDC5 alterations. We expand this phenotypic spectrum to include epileptic spasms, aligning DEPDC5 epilepsies more with the recognized features of other mTORopathies. |
Databáze: | OpenAIRE |
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