|
|||||
|
|
The role of neuronal GABAA receptor subunit mutations in idiopathic generalized epilepsies |
|
| Authors: | L.M. Dibbens L.A. Harkin M. Richards B.L. Hodgson A.L. Clarke S. Petrou I.E. Scheffer S.F. Berkovic J.C. Mulley |
| Affiliation: | 1. Epilepsy Research Program, SA Pathology at Women''s and Children''s Hospital, North Adelaide, South Australia, Australia;2. School of Paediatrics and Reproductive Health (Paediatrics), The University of Adelaide, South Australia, Australia;3. Howard Florey Institute, University of Melbourne, Parkville, Melbourne, Victoria, Australia;4. Department of Medicine and Epilepsy Research Centre, The University of Melbourne, Austin Health, Melbourne, Victoria, Australia;5. Department of Paediatrics, The University of Melbourne, Austin Health and Royal Children''s Hospital, Melbourne, Victoria, Australia;6. Department of Neurosciences, Monash Medical Centre, Melbourne, Victoria, Australia;g School of Molecular and Biomedical Sciences (Genetics), The University of Adelaide, South Australia, Australia |
| Abstract: | Rare GABAA receptor γ2 and α1 subunit mutations of pathogenic effect have been described segregating in families with “monogenic” epilepsies. We now report globally on the genetic variation contained within all 16 neuronal GABAA receptor subunit genes from the one patient cohort. The cohort consists of GEFS+, FS, and IGE subgroups as either sporadic cases or index cases from small families, with one index case from one large IGE family. The rarity of mutations and coding variation in general across all of the subunits suggests a low tolerance for mutations affecting GABA mediated neuronal inhibition. Characterization of the broader channelopathy load associated with susceptibility to these common epilepsies mostly with complex genetics will need to be expanded beyond the family of GABAA receptor subunits to all families of neuronal ion channels and their interacting molecules by systematic mutation detection associated with functional investigation of their naturally occurring genetic variations. |
| Keywords: | Febrile seizures GABAA receptors Genetic epilepsy with febrile seizures plus Genetics Idiopathic generalized epilepsy |
| 本文献已被 ScienceDirect 等数据库收录！ | |