低钾性周期性麻痹一家系及SCN4A基因变异分析

Mutation analysis of SCN4A gene in a family with hypokalemic periodic paralysis

目的探讨低钾性周期性麻痹家系的临床特征及SCN4A基因变异情况。方法收集患者的临床资料,外周血中提取先证者及弟弟、父母DNA,用全外显子测序明确先证者的突变位点,根据变异位点设计特异性引物,用PCR检测突变位点从而进一步明确家系的致病原因。结果患者,男,19岁,汉族,该患者表现周期性麻痹,发作时血钾低,家族中其父亲及爷爷有类似症状,通过基因检测技术在患者SCN4A基因12号外显子检测到1个杂合错义变异(p.R672H),先证者父亲也检测到相同突变。结论本研究发现的SCN4A基因杂合错义变异(p.R672H)导致家族型低钾性周期性麻痹,为患者将来的遗传咨询提供参考,并丰富基因型与临床表现之间关系的研究资料。

Objective To analyze the clinical features and SCN4A gentic background of a family with hypokalemic periodic paralysis.Methods Peripheral blood samples and clinical data were collected from the proband,his brother and parents,and genomic DNA was extracted from these blood samples.Genome-wide exome sequencing was conducted to determine the mutation site in the proband and then allele-specific oligonucleotide primers were designed based on the mutation site.Polymerase chain reaction(PCR)was performed to detect the mutation site to further identify the causative gene in the family.Results The patient was a 19-years-old male,Han nationality.The patient presented with periodic paralysis while hypokalemia at the same time.His father and grandpa have a similar medical history in the family.A hybrid missense variation(p.R672H)was identified in exon 12 of SCN4A gene in the proband.The same mutation was also detect in the proband's father.Conclusions The heterozygous missense variation of SCN4A gene(p.R672H)found in this study resulted in familial hypokalemic periodic paralysis.Our research provided reference for the future genetic counseling of this patient and enriched the research data on the relationship between genotype and clinical manifestations.