MYBPC3 gene variation and clinical phenotypes in familial hypertrophic cardiomyopathy
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摘要: 目的:分析家族性肥厚型心肌病(FHCM)患者心脏肌球蛋白结合蛋白C3(MYBPC3)基因变异及其与临床表型的关系。方法:纳入2016—2018年于福建省立医院就诊的肥厚型心肌病(HCM)10个家系,通过二代测序筛选出携带MYBPC3基因变异的3个家系,收集家系中携带MYBPC3基因变异患者的临床资料,包括家族史、临床表现、心电图及超声心动图,以进行基因型-表型关联分析。结果:3个家系共有19名家系成员,有2名家系成员猝死,8名家系成员携带有MYBPC3基因变异。其中两个家系携带MYBPC3基因c.3624delC杂合缺失变异;1个家系携带MYBPC3基因c.3369_3370insC变异,该家系其他家系成员携带ACTN2、CACNA1C、DTNA、TTN基因变异。在这3个家系中,4例患者在40岁以前发病,其中1例患者23岁时猝死;3例患者以室间隔增厚为主,合并左室流出道梗阻,4例患者室间隔及左室壁均有增厚但程度较轻,无左室流出道梗阻;1例患者合并心房颤动,2例患者有室性期前收缩。结论:MYBPC3基因不同位点的突变可导致FHCM,同一家族的HCM患者可能有不同的基因变异位点。MYBPC3基因c.3369_3370insC变异为首次发现的致病基因变异。与以前的报道不同,本研究发现有MYBPC3基因变异的HCM患者发病早,病情进展快,临床预后差。Abstract: Objective: To analyze myosin-binding protein(C3 MYBPC3) gene variation in patients with familial hypertrophic cardiomyopathy(FHCM) and the relationship with clinical phenotypes.Methods: Among ten families with hypertrophic cardiomyopathy(HCM) treated in Fujian Provincial Hospital from 2016 to 2018, three harbored MYBPC3 mutations were screened out using second-generation sequencing. Clinical data, including family history, clinical manifestations, electrocardiogram, and echocardiography of patients with MYBPC3 gene mutation in families were extracted to analyze the association between genotype and clinical phenotype.Results: Among the 19 members from these three families, two had a sudden death, and eight carried the MYBPC3 mutation. Two of the three families carried the.3624 delC heterozygous deletion variant of MYBPC3 gene; the third family carried the c.3369_3370 insC mutation of the MYBPC3 gene, and other members of this family carried mutations of ACTN2, CACNA1 C, DTNA, and TTN genes. Among the three families, four patients had an overt clinical manifestation before 40 years old. One of them had a sudden death at 23 years old; Three patients had interventricular septal thickening and left ventricular outflow tract obstruction. Four patients had mild interventricular septal thickening and left ventricular wall thickening but to a lesser extent without left ventricular outflow tract obstruction. One patient had atrial fibrillation. Two patients had ventricular premature beats.Conclusion: Mutations at different loci in the MYBPC3 gene can lead to FHCM, and HCM patients in the same family may have different gene variation loci. The mutation of MYBPC3 gene c.3369_3370 insC is found for the first time. Unlike previous reports, we find that HCM patients with MYBPC3 gene variations can have early onset, rapid disease progression, and poor clinical prognosis.
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Key words:
- hypertrophic cardiomyopathy /
- MYBPC3 /
- clinical phenotype /
- gene variation
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