家族性低钾型周期性麻痹的基因突变与临床特征

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.

Correlating phenotype and genotype in the familial hypokalaemic periodic paralysis

Objective To inquire into the location of the relevant gene mutations in the Chinese familial hypokalaemic periodic paralysis, and to specify the correlation between the genotype and the clinical features of this disease. Methods Target-exon PCR and DNA direct sequencing were used to research the mutations in the CACNA1S, SCN4A, and KCNE3 genes of 14 familial hypokalaemic periodic paralysis probands. If a positive member was found, the other members of his (her) family must be inspected with the sequencing method. Results The probands of 3 families showed the known correlating mutations of hypokalaemic periodic paralysis, which were R1239H mutations in the CACNA1S in 1 family and R672H mutations in the SCN4A in the other 2 families. In addition, the differences of the age of onset, the responsibility to the treatment with acetazolamide and penetrance were found between the CACNA1S R1239H and SCN4A R672H mutations. Conclusions SCN4A R672H and CACNA1S R1239H mutations exist in the Chinese familial hypokalaemic periodic paralysis. Differences of the clinical features exist, resulting from these 2 kinds of mutations.