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目的低钾周期性麻痹(hypokalemic periodic paralysis,HoKPP)是一种由于离子通道功能异常引起的疾病,呈常染色体显性遗传。文中筛查HoKPP家系患者的基因突变位点,为产前基因诊断提供实验依据。方法报告1个具有4代18例患者的HoKPP中国家系。提取HoKPP患者、家系中健康人以及100例无血缘正常对照血样中白细胞基因组DNA,应用PCR和DNA测序进行候选基因突变分析,包括骨骼肌二氢嘧啶敏感性钙通道α1亚单位(CACNA1S)基因和骨骼肌钠通道α亚单位基因(SCN4A)。结果分子遗传学研究显示该HoKPP家系所有患者CACNA1S基因外显子30上均存在杂合突变(G3716A),推测导致氨基酸序列改变(R1239H),家系中健康人以及无血缘正常对照组中均未见患者所携带的杂合突变位点(G3716A)。结论 CACNA1S基因的R1239H突变是该HoKPP家系发病的分子遗传学基础,可行产前基因诊断预防患儿出生。
Objective Hypokalemic periodic paralysis (HoKPP) is an autosomal dominant inheritance of diseases caused by dysfunction of ion channels. The screening of gene mutations in patients with HoKPP pedigree in the article provides experimental evidence for prenatal genetic diagnosis. Methods One HoKPP Chinese pedigree with 4 generations of 18 patients was reported. Leukocyte genomic DNA was extracted from HoKPP patients, healthy family members and 100 unrelated healthy blood samples. Candidate gene mutations were analyzed by PCR and DNA sequencing, including skeletal dihydropyrimidine-sensitive calcium channel α1 subunit (CACNA1S) gene and Skeletal Na + channel alpha subunit gene (SCN4A). Results Molecular genetic studies showed that there was a heterozygous mutation (G3716A) in exon 30 of CACNA1S gene in all patients with this HoKPP pedigree, which was presumed to result in a change of amino acid sequence (R1239H), not seen in healthy family members and unrelated normal control subjects Heterozygous mutation site (G3716A) carried by the patient. Conclusion The R1239H mutation of CACNA1S gene is the molecular genetic basis of the onset of HoKPP pedigree. It is feasible to diagnose the birth of children with prenatal gene diagnosis.