一个患有热性惊厥附加症的全身性癫痫家族中γ-氨基丁酸A（GABA(A)）受体γ2亚基的截短现象
Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus.
作者信息
Harkin Louise A, Bowser David N, Dibbens Leanne M, Singh Rita, Phillips Fiona, Wallace Robyn H, Richards Michaella C, Williams David A, Mulley John C, Berkovic Samuel F, Scheffer Ingrid E, Petrou Steven
机构信息
Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, Adelaide, South Australia, Australia.
出版信息
Am J Hum Genet. 2002 Feb;70(2):530-6. doi: 10.1086/338710. Epub 2001 Dec 17.
Recent findings from studies of two families have shown that mutations in the GABA(A)-receptor gamma2 subunit are associated with generalized epilepsies and febrile seizures. Here we describe a family that has generalized epilepsy with febrile seizures plus (GEFS(+)), including an individual with severe myoclonic epilepsy of infancy, in whom a third GABA(A)-receptor gamma2-subunit mutation was found. This mutation lies in the intracellular loop between the third and fourth transmembrane domains of the GABA(A)-receptor gamma2 subunit and introduces a premature stop codon at Q351 in the mature protein. GABA sensitivity in Xenopus laevis oocytes expressing the mutant gamma2(Q351X) subunit is completely abolished, and fluorescent-microscopy studies have shown that receptors containing GFP-labeled gamma2(Q351X) protein are retained in the lumen of the endoplasmic reticulum. This finding reinforces the involvement of GABA(A) receptors in epilepsy.
对两个家族的研究最近发现，γ-氨基丁酸A（GABA(A)）受体γ2亚基的突变与全身性癫痫和热性惊厥有关。在此，我们描述了一个患有伴有热性惊厥附加症的全身性癫痫（GEFS(+)）的家族，其中包括一名患有婴儿严重肌阵挛癫痫的个体，在该个体中发现了第三个GABA(A)受体γ2亚基突变。此突变位于GABA(A)受体γ2亚基的第三和第四跨膜结构域之间的细胞内环中，并在成熟蛋白的Q351处引入了一个提前终止密码子。表达突变型γ2(Q351X)亚基的非洲爪蟾卵母细胞中的GABA敏感性完全丧失，荧光显微镜研究表明，含有绿色荧光蛋白标记的γ2(Q351X)蛋白的受体保留在内质网腔中。这一发现进一步证明了GABA(A)受体与癫痫有关。
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