Correlation analysis between p.R616C mutation of JPH2 gene and familial dilated cardiomyopathy
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摘要: 目的 对1例家族性扩张型心肌病(dilated cardiomyopathy，DCM)家系进行致病基因筛查，分析其基因型与表型的相关性。方法 研究对象为1例DCM先证者及其家系成员，另选取体检中心健康成年人为对照。收集先证者家系的临床资料，对先证者及发病家系成员进行全基因组测序，筛选可疑致病基因，并通过Sanger测序法进行验证。对其他家系成员及对照组进行相关基因筛查。结果 对该家系筛查发现包括先证者在内的5例DCM患者，且基因检测发现均存在JPH2基因的c.1846C>T(p.Arg616Cys)突变，另有1例无临床表型的突变基因携带者。余家系成员及对照组相同位点未见异常。在随访过程中先证者出现恶性心律失常。结论 本研究发现JPH2基因的p.R616C突变可能导致家族性DCM，且该基因突变可能为恶性基因突变。Abstract: Objective The aim was to screen the pathogenic genes and analyze the genotype-phenotype correlation in a pedigree with dilated cardiomyopathy.Methods The proband with dilated cardiomyopathy(DCM)and his family members were included in this study, while healthy controls from physical examination centers were selected. Clinical data were collected through genetic counseling. The whole genome testing was carried out to screen for suspected pathogenic genes in the proband and affected members. Candidate mutations were further confirmed by Sanger sequencing. Genetic testing was performed on other family members and controls.Results Five patients with DCM were identified in this family, and the same mutation in the JPH2 gene(c.1846C>T/p.Arg616Cys) was found in all of them. There was also one carrier with no obvious clinical phenotype. This variant was absent in other family members and controls. The proband developed malignant arrhythmia during follow-up.Conclusion In this study, we find that JPH2 p.R616C variant probably contributes to familial dilated cardiomyopathy, and the mutation may be malignant.
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Key words:
- dilated cardiomyopathy /
- JPH2 /
- gene mutation
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图 6 不同种属JPH2蛋白序列对比
Figure 6. Alignment of multiple JPH2 protein sequences across species
表 1 先证者家系临床资料
Table 1. Clinical data of the proband's family
成员 性别 年龄/岁 症状 ECG UCG CMR纤维化 LVEDd/mm LVEF/% Ⅱ-1 男 67 活动后胸闷气喘 房颤 71 13 + Ⅱ-5 女 61 活动后胸闷气喘 窦性心律；ST-T改变 59 34 未做 Ⅱ-9 女 55 心慌伴胸闷气喘 窦性心律；室性期前收缩 57 40 + Ⅲ-1 男 43 活动后胸闷气喘 窦性心律 80 19 + Ⅲ-3 女 41 - 窦性心律 54 43 - Ⅳ-3 女 19 - 窦性心律 45 64 未做 
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