The relationship between double-gene mutation of DSP and familial hypertrophic cardiomyopathy
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摘要: 目的 对导致肥厚型心肌病(HCM)的2种新型桥粒斑蛋白基因(DSP)基因突变进行研究，并初步分析家族性HCM基因型与临床表型的关系。方法 纳入1例HCM先证者及其家系成员，同时选取100例健康人作为对照。采集先证者及其家系成员的临床资料，对该家系及对照组成员开展基因测序确定致病基因，最后绘制家系图谱进行分析。结果 该家系中，先证者及其父亲确诊为HCM，基因测序提示2人均携带DSP c.6799A>T(p.Thr2267Ser)和c.8044C>G(p.Gln2682Glu)两种错义突变，先证者的2个女儿分别携带1种DSP错义突变，其余家属及健康对照组无此两种突变。结论 新发现的DSP基因突变可能是家族性HCM的致病突变，携带多个基因突变的家系成员可能更易患病，确切发病机制还需进一步研究。Abstract: Objective To investigate two novel DSP gene mutations leading to hypertrophic cardiomyopathy(HCM), and elucidate the correlation between genotypes and clinical phenotypes in familiar HCM.Methods One HCM proband and his family members were enrolled while 100 healthy people were selected as the control. Clinical data were collected from the HCM patient's family. Gene sequencing was carried out for the family and controls to identify the pathogenic gene. Finally, the family tree was constructed and the pertinence was performed on genotypes and clinical phenotypes.Results In all of this family, the propositus and his father, carried c.6799A>T missense mutations(p.Thr2267Ser) and c.8044C>G missense mutations(p.Gln2682Glu) of the DSP gene in the meanwhile, were diagnosed as HCM. The two daughters of the propositus carried one missense mutation of the DSP gene separately. The rest of the family members and healthy controls had no such mutations.Conclusion The novel DSP gene mutations may be the pathogenic mutations of familiar HCM. Family members carrying compound mutations are more likely to develop hypertrophic cardiomyopathy, but the exact pathogenesis still needs further study.
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Key words:
- hypertrophic cardiomyopathy /
- DSP /
- gene mutation /
- heterogeneity
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