Dibbens L M, Harkin L A, Richards M, Hodgson B L, Clarke A L, Petrou S, Scheffer I E, Berkovic S F, Mulley J C
Epilepsy Research Program, SA Pathology at Women's and Children's Hospital, North Adelaide, South Australia, Australia.
Neurosci Lett. 2009 Apr 10;453(3):162-5. doi: 10.1016/j.neulet.2009.02.038. Epub 2009 Feb 21.
Rare GABA(A) receptor gamma2 and alpha1 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 GABA(A) 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 GABA(A) 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.
已描述了具有致病作用的罕见GABA(A)受体γ2和α1亚基突变在患有“单基因”癫痫的家族中分离。我们现在全面报告来自同一患者队列的所有16个神经元GABA(A)受体亚基基因中的遗传变异。该队列包括GEFS(+)、FS和IGE亚组，分别为散发病例或来自小家庭的索引病例，其中有一例来自一个大型IGE家族的索引病例。所有亚基中突变和编码变异总体上都很罕见，这表明对影响GABA介导的神经元抑制的突变耐受性较低。对于这些大多具有复杂遗传学的常见癫痫易感性相关的更广泛通道病负荷的表征，需要通过与对其天然存在的遗传变异进行功能研究相关的系统突变检测，从GABA(A)受体亚基家族扩展到所有神经元离子通道家族及其相互作用分子。
