低钾型周期性麻痹患者的临床及基因特征

Clinical and Genetic Features of Hypokalemic Periodic Paralysis

目的分析低钾型周期性麻痹患者的临床特征及基因突变特点。方法对32例低钾型周期性麻痹患者进行基因筛查,发现6例存在基因突变,回顾性分析这6例患者的临床及基因特征,并进行家系研究。基因检测应用聚合酶链式反应后直接测序。结果 6例患者均青少年发病,5例发作有明确诱因,检测血钾低且补钾治疗有效。5例患者有明确低钾型周期性麻痹家族史。患者基因突变分别为CACNA1S基因c.1583G>A(p.Arg528His)、c.2627T>A(p.Val876Glu)、c.2690G>A(p.Arg897Met)及c.2700G>C(p.Arg900Ser)突变以及SCN4A基因c.2015G>A(p.Arg672His)和c.2024G>A(p.Arg675Gln)突变,其中CACNA1S基因p.Arg528His和SCN4A基因p.Arg672His为热点突变,Arg897Met为新的突变位点。结论 6例低钾型周期性麻痹患者临床表现典型,存在CACNA1S或SCN4A基因的胚系突变,CACNA1S Arg897Met为新的突变位点。

Objective To analyze clinical features and gene mutations of patients with hypokalemic periodic paralysis. Methods Gene sequencing in 32 patients with hypokalemic periodic paralysis revealed gene mutation in six patients. Clinical data of the six cases and their families＇ profiles were analyzed retrospectively. Gene mutation was determined by polymerase chain reaction and sequencing. Results All of the six patients were attacked by periodic paralysis with decreased serum potassium level in adolescence, and five patients had significant inducement before the attacks. Potassium supplements were effeetive in relieving symptom and raising serum potassium levels. Five patients had a family history of hypokalemic periodic paralysis. The patients had genetic mutations including CACNA1Sc. 1583G 〉 A（ p. Arg528His）, e. 2627T 〉 A（ p. Va1876Glu）, c. 2690G 〉 A（ p. Arg897Met）, c. 2700G 〉 c（ p. Arg900Ser） and SCN4A c. 2015G 〉 A （p. Arg672His） , c. 2024G 〉 A （p. Arg675Gln）. CACNA1S p. Arg528His and SCN4A p. Arg672His are hotspots, and CACNA1S Arg897Met was novel mutation. Conclusion All of the six patients have typical clinical manifestations, as well as germline mutation of CACNA1S gene or SCN4A gene. CACNA1S Arg897Met is novel mutation.