伴赖氨酸缺乏蛋白激酶1基因错义突变的高血压1例的临床特征及家系分析

Clinical characteristics and pedigree analysis of a hypertension patient with with-no-lysine kinase 1 gene missense mutation

目的本文对1例早发高血压Gordon综合征患者进行家系调查和基因检测,以明确患者的临床诊断和致病基因是否为家族遗传性,并探讨该突变类型与表现型的关系。方法收集先证者及其家系的临床资料,提取外周血基因组DNA,对赖氨酸缺乏蛋白激酶1(WNK1)基因突变进行检测。采用聚合酶链反应(PCR)对WNK1进行分子分析。对确诊患者给予限盐和口服氢氯噻嗪治疗并对其进行随访。结果本研究纳入包括先证者在内的8名家系成员。先证者及两名家系成员携带有WNK1基因C.3154G>A错义突变,该突变为首次报道。该突变先证者出现早发高血压和早发脑卒中事件,对先证者给予限盐和口服氢氯噻嗪治疗,治疗1个月和3个月后随访发现疗效显著且稳定。结论本研究通过对早发高血压病例进行家系研究和突变基因检测,发现了WNK1基因一个新的致病突变。

Objective To analyze the gene mutation of early-onset hypertension, to clarify the patient’s clinical diagnosis and whether the disease-causing gene is hereditary, and to examine the relationship between the mutation type and phenotype. Methods Clinical investigation of the proband and the families was conducted. Genomic DNA was extracted from peripheral blood, gene mutation of with-no-lysine kinase 1(WNK1) was detected.Polymerase chain reaction(PCR) was used to implement molecular analysis of WNK1. The PCR products were purified and sequenced to examine the genetic structure. Patients with disease-causing mutations were treated with salt-restriction diet and thiazide diuretics and followed-up. Results The proband and 8 family members were included in this study. A novel missense WNK1 mutation in exon 9, C.3154 G>A, was detected in the proband and 2 family members. Early-onset hypertension and stroke were observed in the proband, and good responses to thiazide diuretics and salt-restriction diet were observed in one-month and three-month follow-up. Conclusion A novel pathogenic mutation of WNK1 gene was identified by pedigree research and DNA screening.