儿童失神癫痫和热性惊厥中的突变γ-氨基丁酸A（GABA(A)）受体γ2亚基

Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures.

作者信息

Wallace R H, Marini C, Petrou S, Harkin L A, Bowser D N, Panchal R G, Williams D A, Sutherland G R, Mulley J C, Scheffer I E, Berkovic S F

机构信息

Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia, Australia.

出版信息

Nat Genet. 2001 May;28(1):49-52. doi: 10.1038/ng0501-49.

DOI:10.1038/ng0501-49

PMID:11326275

Abstract

Epilepsies affect at least 2% of the population at some time in life, and many forms have genetic determinants. We have found a mutation in a gene encoding a GABA(A) receptor subunit in a large family with epilepsy. The two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS). There is a recognized genetic relationship between FS and CAE, yet the two syndromes have different ages of onset, and the physiology of absences and convulsions is distinct. This suggests the mutation has age-dependent effects on different neuronal networks that influence the expression of these clinically distinct, but genetically related, epilepsy phenotypes. We found that the mutation in GABRG2 (encoding the gamma2-subunit) abolished in vitro sensitivity to diazepam, raising the possibility that endozepines do in fact exist and have a physiological role in preventing seizures.

摘要

癫痫在人生的某个阶段会影响至少2%的人口，而且许多类型都有遗传决定因素。我们在一个患有癫痫的大家族中发现了一个编码γ-氨基丁酸A型（GABA(A)）受体亚基的基因突变。两种主要的表型是儿童失神癫痫（CAE）和热性惊厥（FS）。热性惊厥和儿童失神癫痫之间存在公认的遗传关系，但这两种综合征有不同的发病年龄，失神发作和惊厥的生理机制也不同。这表明该突变对不同的神经网络有年龄依赖性影响，这些神经网络影响了这些临床症状不同但有遗传关联的癫痫表型的表达。我们发现，GABRG2（编码γ2亚基）中的突变消除了体外对安定的敏感性，这增加了内源性苯二氮䓬类物质确实存在且在预防癫痫发作中具有生理作用的可能性。