T型钙通道基因CACNA1H是儿童失神癫的易感基因

T-type calcium channel gene-CACNA1H is as usceptibility gene to childhood absence epilepsy

目的 在既往工作的基础上，进一步明确T型钙通道CACNA1H基因是否为儿童失神癫痫(CAE)的易感基因。方法 本组48例，分别来源于北京大学第一医院、首都医科大学附属北京儿童医院、首都儿科研究所附属医院以及山西省儿童医院。对本组患儿进行T型钙通道CACNAlH基因外显子6-12及其相邻的部分内含子PCR产物测序，寻找突变。96个正常对照来自同一地区的无关个体，均无癫痫病史或遗传病家族史。结果 共发现13个单核苷酸多态性，还发现4个突变位点只在CAE中出现，其中2个为错义突变：G773D和HS15Y，均为杂合突变。突变H515Y是新发现的错义突变，患儿从其母亲接受该突变。G773D在第3个CAE家系中发现相同的突变，本例从其父亲接受该突变。结论 T型钙通道CACNA1H基因很可能是CAE的易感基因。

Objective Childhood absence epile ps y (CAE) is one of the most frequently recognized syndromes among the idiopathic generalized epilepsies (IGEs). It is considered to be a hereditary disease. The possible inheritance pattern of CAE is polygenic. The genes responsible for CAE, however, have not yet been identified. The aim of this study was to further inv estigate based on the authors′ recent work whether or not T-type calcium chann el gene-CACNA1H is a susceptibility gene to childhood absence epilepsy. Methods The authors conducted the mutation screening of the exons 6-12 and the nearby partial introns of the CACNA1H gene using the me thod of direct sequencing of PCR products in 48 newly found CAE patients.Results The authors found 13 single nucleotide polymorphi sms (SNPs). They also found 4 mutations which only existed in CAE patients. Both G773D and H515Y mutations were heterozygous. The mutation of H515Y has never b een reported previously. The patient inherited the mutation from his mother. The authors found two CAE patients with the mutation of G773D previously. This is t he third time that the authors found one more CAE family with this G773D mutatio n, and the patient with the mutation G773D inherited the mutation from his fathe r.Conclusion T-type calcium channel gene-CACNA1H might be a susceptibility gene to childhood absence epilepsy.