一个中国家族性低钾型周期性麻痹家系中的CACNA1S基因R1239H突变

目的筛查家族性低钾型周期性麻痹（hypokalaemic periodic paralysis，HOKPP）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PCR和DNA测序技术，对1个HOKPP家系（包括2例患者共11名成员）进行候选基因CACNA1S和SCN4A的筛查，并总结该家系患者的临床特点。结果此家系的2例患者符合HOKPP的诊断标准，突出特点为：儿童期发病，青春期加重，成年后病情减轻；女性在月经前期好发，而妊娠期无发作；钾剂和乙酰唑胺治疗有效。DNA测序结果发现2例患者的CACNA1S基因第30外显子上均存在3716（G→A）杂合突变，导致氨基酸序列改变R1239H，家族其他成员未见此突变。结论中国家族性HOKPP存在CACNA1S基因R1239H突变。

R1239H mutation of CACNA1S gene in a Chinese family with hypokalaemic periodic paralysis

OBJECTIVE: Mutation screening was performed to a Chinese family with hypokalaemic periodic paraiysis(HOKPP) for locating the corresponding mutations of gene and for specifying the clinical features associated with mutations. METHODS: The cilnical features of patients from HOKPP family were summurized. Techniques of target exon PCR and direct sequencing were used to screen the mutation in CACNA1S and SCN4A genes in all numbers of the family. RESULTS: Two patients of the family showed the typical features of HOKPP: the age of disease onset is during the childhood, acetazolamide is effective to patients treated. A heterozygous point mutation 3716 (G>A) causing R1239H was found in exon 30 of CACNA1S gene of the patients, but not found in normal members of the family. CONCLUSION: The mutant R1239H in CACNA1S gene exists in Chinese patients with familial hypokalaemic periodic paralysis.