低钾周期性麻痹家系CACNA1S基因突变的研究

摘要

目的 低钾周期性麻痹(hypokalemic periodic paralysis,HoKPP)是一种由于离子通道功能异常引起的疾病,呈常染色体显性遗传.文中筛查HoKPP家系患者的基因突变位点,为产前基因诊断提供实验依据.方法 报告1个具有4代18例患者的HoKPP中国家系.提取HoKPP患者、家系中健康人以及100例无血缘正常对照血样中白细胞基因组DNA,应用PCR和DNA测序进行候选基因突变分析,包括骨骼肌二氢嘧啶敏感性钙通道α1亚单位(CACNA1S)基因和骨骼肌钠通道α亚单位基因(SCN4A).结果 分子遗传学研究显示该HoKPP家系所有患者CACNA1S基因外显子30上均存在杂合突变(G3716A),推测导致氨基酸序列改变(R1239H),家系中健康人以及无血缘正常对照组中均未见患者所携带的杂合突变位点(G3716A).结论 CACNA1S基因的R1239H突变是该HoKPP家系发病的分子遗传学基础,可行产前基因诊断预防患儿出生.%Objective Hypokalemic periodic paralysis ( HOKPP ) is an autosomal dominant disorder belonging to a group of muscle diseases involving the abnormal function of ion channels. This study aimed to screen gene mutations in a Chinese HOKPP family for prenatal gene diagnosis. Methods DNA was extracted from the blood samples of 18 affected individuals of a four-generation Chinese HOKPP family, unaffected relatives of the family and 100 normal controls. The disease-causing mutation was analyzed by poly-merase chain reaction ( PCR ) and DNA sequencing of candidate genes, including the al subunit of the dihydropyridine receptor calcium channel gene ( CACNA1S ) and skeletal muscle sodium channel gene ( SCN4A ). Results There was a heterozygous mutation ( G3716 A ) on exon 30 of the CACNA1S gene in all the patients of the family, resulting in a predicted change of amino acid sequence ( R1239H ), but no mutation was found on this site in the other healthy family members and 100 normal controls. Conclusion Mutation of the CACNA1S gene ( R1239H ) is the molecular basis of the HOKPP family, which necessitates prenatal gene diagnosis for HOKPP.