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目的筛查家族性低钾型周期性麻痹相关基因突变位点,总结该病基因型和临床表型的相关性。方法应用聚合酶链反应(PCR)和DNA测序技术,对14个家族性低钾型周期性麻痹家系中的14例先证者进行候选基因CACNA1S、SCN4A、KCNE3的筛查,阳性者再对其家系中其他患者和健康亲属进行测序分析。结果14个家系中有3个家系其先证者存在已知的低钾型周期性麻痹相关突变(1个家系发生CACNA1S基因R1239H突变,2个家系发生SCN4A基因的R672H突变)。进一步对3个突变家系中4例其他患者和34名健康亲属测序分析发现,R1239H突变为完全外显率,R672H突变为不全外显率。同时还发现2种突变在发病年龄和乙酰唑胺的疗效等方面存在差异。结论中国低钾型周期性麻痹患者存在CACNA1S基因R1239H和SCN4A基因的R672H突变,2种突变的临床表型存在差异。
Objective To screen the mutations of familial hypokalemic periodic paralysis-related genes and summarize the correlation between the genotype and clinical phenotype of the disease. Methods 14 cases of familial hypokalemic periodical paralysis pedigree were probed with CACNA1S, SCN4A and KCNE3 candidate genes by polymerase chain reaction (PCR) and DNA sequencing. Other patients in the pedigree and health relatives were sequenced. Results Three of the 14 pedigrees had known hypokalemic periodic paralysis-associated mutations (R1239H mutation of CACNA1S gene in one pedigree and R672H mutation of SCN4A gene in two pedigrees). Further sequencing of 4 other patients and 34 healthy relatives in 3 mutant pedigrees revealed that R1239H was mutated to complete penetrance and R672H to incomplete penetrance. Also found two kinds of mutations in the age of onset and the efficacy of acetazolamide there are differences. Conclusions The R672H mutation of CACNA1S gene R1239H and SCN4A genes is present in patients with hypokalemic periodic paralysis in China. The clinical phenotypes of the two mutations are different.