Li H Y, Zhou X L, Guo J F, Tang B S, Fu Y J, Sun J Y
Department of Neurology, the People's Hospital of Anyang City, Anyang 455000, China.
Department of Neurology, Xiangya Hospitial, Central South University, Changsha 410008, China.
Zhonghua Yi Xue Za Zhi. 2020 Dec 8;100(45):3622-3625. doi: 10.3760/cma.j.cn112137-20200421-01265.
To report a Chinese family with hypokalemic periodic paralysis (HOKPP) and investigate the clinical and pathogenic gene characteristics of the family. The clinical, electrophysiological and pathological data of the proband of the family were analyzed, and the information of the family was investigated in detail. The peripheral venous blood of the six members of the family was collected and their genomic DNA was extracted. The genes related to periodic paralysis analysis of the proband were performed by the second generation sequencing. The pathogenicity of the mutant protein was respectively analyzed by the bioinformatics software SIFT, Polyphen2 and Mutation Tasker. The cosegregation analysis of phenotype and genotype of the family was performed by the first generation sequencing. There were 3 patients in the family with the onset age of 21 to 42 years old. All the patients manifested with vomiting as the first symptoms, then presented with muscle weakness accompanied by muscle soreness. The muscle weakness gradually relieved in 3 to 5 days. Creatine kinase (CK) of the proband significantly increased. Electromyographic exercise test was positive, however, electromyography and muscle pathological analysis were normal. The genes related to periodic paralysis analysis of the proband found a novel mutation (c.2458A>T (p.N.820Y)) of SCN4A gene which was located in the conservative region. The function analysis showed it was a pathogenic mutation. Moreover, the first generation sequencing confirmed that the mutation was cosegregated with patients in the family. Meanwhile, it was found that the proband's son carried the same mutation, but without any symptom, indicating that he was a pre-symptomatic patient. Vomiting can be one of the symptoms of the patients with HOKPP. The novel mutation of SCN4A gene c.2458 A>T is the pathogenic mutation of the family. Patients with periodic paralysis should be tested for blood potassium and genes as early as possible to facilitate early diagnosis and genetic counseling.
报道一个低钾性周期性麻痹（HOKPP）的中国家系，并研究该家系的临床和致病基因特征。分析该家系先证者的临床、电生理和病理资料，并详细调查家系信息。采集家系6名成员的外周静脉血，提取基因组DNA。通过二代测序对先证者进行周期性麻痹相关基因分析。利用生物信息学软件SIFT、Polyphen2和Mutation Tasker分别分析突变蛋白的致病性。通过一代测序对该家系的表型和基因型进行共分离分析。该家系有3例患者，发病年龄为21至42岁。所有患者均以呕吐为首发症状，随后出现肌无力并伴有肌肉酸痛。肌无力在3至5天内逐渐缓解。先证者的肌酸激酶（CK）显著升高。肌电图运动试验阳性，但肌电图和肌肉病理分析正常。先证者的周期性麻痹相关基因分析发现SCN4A基因有一个新的突变（c.2458A>T（p.N.820Y）），位于保守区域。功能分析表明这是一个致病突变。此外，一代测序证实该突变与家系中的患者共分离。同时发现先证者的儿子携带相同突变，但无任何症状，表明他是一名症状前患者。呕吐可能是HOKPP患者的症状之一。SCN4A基因c.2458 A>T的新突变是该家系的致病突变。周期性麻痹患者应尽早进行血钾和基因检测，以利于早期诊断和遗传咨询。
