Childhood absence epilepsy and febrile seizures:: a family with a GABAA receptor mutation
Childhood absence epilepsy and febrile seizures:: a family with a GABAA receptor mutation
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DOI：
10.1093/brain/awg018
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发表时间：
2003-01-01
期刊：
影响因子：
14.5
通讯作者：
Berkovic, SF
中科院分区：
文献类型：
--
作者：
Marini, C;Harkin, LA;Berkovic, SF
虽然从简单孟德尔遗传的家族中发现了一些特发性癫痫的基因，但遗传复杂的普通特发性广泛性癫痫的基因目前还难以捉摸。我们研究了一个癫痫大家庭，其中两种主要表型是儿童期缺失癫痫（CAE）和发热性癫痫发作（FS），这为鉴定癫痫基因提供了特殊的机会。在四代人的时间里，共有35名家族成员患过癫痫。表型为典型CAE（8例）；单纯发热性惊厥（15例）、发热性惊厥加（FS+）（3例）；肌阵挛性不稳定癫痫（2例）；全身性癫痫伴强直阵挛发作（1例）；部分性癫痫（1例）；和未分类癫痫，尽管评估(2)。其余三个人没有任何信息。FS以常染色体显性方式遗传，外显率为75%。该家族CAE的遗传不是简单的孟德尔遗传，而是至少涉及两个基因的复杂遗传。5号染色体上的GABA(A)受体gamma2亚基基因突变与FS、FS+和CAE分离，也发生在其他表型的个体中。临床和分子数据表明，GABA(A)受体亚基突变可以单独解释FS表型。该基因与另一个或多个基因的相互作用是该家族CAE表型所必需的。对另一个可能导致CAE表型的基因的连锁分析表明，该基因可能位于10、13、14和15号染色体上。在其他缺失谱系中检查这些基因座是有必要的。
Although several genes for idiopathic epilepsies from families with simple Mendelian inheritance have been found, genes for the common idiopathic generalized epilepsies, where inheritance is complex, presently are elusive. We studied a large family with epilepsy where the two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS), which offered a special opportunity to identify epilepsy genes. A total of 35 family members had seizures over four generations. The phenotypes comprised typical CAE (eight individuals); FS alone (15), febrile seizures plus (FS+) (three); myoclonic astatic epilepsy (two); generalized epilepsy with tonic-clonic seizures alone (one); partial epilepsy (one); and unclassified epilepsy despite evaluation (two). In three remaining individuals, no information was available. FS were inherited in an autosomal dominant fashion with 75% penetrance. The inheritance of CAE in this family was not simple Mendelian, but suggestive of complex inheritance with the involvement of at least two genes. A GABA(A) receptor gamma2 subunit gene mutation on chromosome 5 segregated with FS, FS+ and CAE, and also occurred in individuals with the other phenotypes. The clinical and molecular data suggest that the GABA(A) receptor subunit mutation alone can account for the FS phenotype. An interaction of this gene with another gene or genes is required for the CAE phenotype in this family. Linkage analysis for a putative second gene contributing to the CAE phenotype suggested possible loci on chromosomes 10, 13, 14 and 15. Examination of these loci in other absence pedigrees is warranted.