Multiplex families with epilepsy: success of clinical and molecular genetic characterization
| Autor: | Aziz Mazarib, Zaid Afawi, Rachel Straussberg, Sarah E. Heron, Marie Mangelsdorf, Samuel F. Berkovic, Melanie Bahlo, Adel Misk, Dana Ekstein, Karen Oliver, Jozef Gecz, Hadassa Goldberg-Stern, Miriam Y. Neufeld, Heather C Mefford, Robyn Heather Wallace, Zamir Shorer, Simri Walid, Gemma L. Carvill, Leanne M. Dibbens, Bruria Ben-Zeev, James N. Macpherson, Esther Kahana, John C. Mulley, Tally Lerman-Sagie, Mark A. Corbett, Uri Kramer, Sara Kivity, Katherine L. Helbig, Ilan Blatt, Amos D. Korczyn, Graeme D. Jackson, Ingrid E. Scheffer, Rafik Masalha, Muhammad Mahajnah |
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| Přispěvatelé: | Afawi, Zaid, Oliver, Karen L, Kivity, Sara, Mazarib, Aziz, Heron, Sarah E, Dibbens, Leanne M, Berkovic, Samuel F |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine experimental Progressive myoclonus epilepsy Biology Article Cohort Studies 03 medical and health sciences Epilepsy 0302 clinical medicine Dravet syndrome Febrile seizure medicine Humans Inheritance Patterns Family Genetic Predisposition to Disease Genetic Testing Israel Generalized epilepsy theoretical Genetic testing Genetics medicine.diagnostic_test behavioural finance medicine.disease ecological finance Pedigree 030104 developmental biology Epilepsy syndromes Female Neurology (clinical) 030217 neurology & neurosurgery |
| Popis: | Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis. Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate. Results: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A , KCNQ2 , CSTB ), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1 , PCDH19 , TBC1D24 ). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically. Conclusion: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies. |
| Databáze: | OpenAIRE |
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