一个家族性肥厚型心肌病家系基因突变位点分析

Analysis of gene mutations in a family with hypertrophic cardiomyopathy

目的:研究一个家族性肥厚型心肌病家系的基因突变,并初步分析临床表型与其基因突变的关系。方法:家系调查收集临床资料,采集家系成员外周血,提取基因组DNA,进行高通量测序确定突变基因位点,并结合生物信息学技术分析。结果:此家系3代7人中,确诊为肥厚型心肌病的患者有4例,只有两例临床症状明显且发病较晚,另外两例均无明显临床症状。系谱中每一代均有患者,男女均可患病。家系中明确两例患者MYBPC3基因上第16外显子存在c.1504位置上胞嘧啶到胸腺嘧啶的杂合改变。经生物信息学分析,此位点突变可能有害。结论:肥厚型心肌病为常染色体显性遗传病,同一家族患者之间其临床表型存在明显的异质性,MYBPC3基因上c.1504C>Tp.(Arg502Trp)的突变可能是该家系的致病原因。

Objective:Study sought to determine the frequency and phenotype of mutation in patients with hypertrophic cardiomyopathy.Method:Clinical data were collected.Genomic DNA was extracted from the peripheral blood samples of family members.High-throughput sequencing and bioinformatics approaches were applied to analyze mutant sites.Result:In all of this family,four members were identified as HCM patients.But phenotypic expression can vary even within the same family.Two of the patients were associated with apparent symptoms,having later onset.There was a patient in each generation,both male and female suffered from this disease.Though the gene testing,the female proband and her son were found heterozygous mutations of the MYBPC3 gene at Exo16 (c.1504 C>T).After analysis this mutation maybe deleterious.Conclusion:Hypertrophic cardiomyopathy was autosomal dominant inheritance.Although the same mutation in this family,clinical outcomes of HCM are highly variable.The heterozygous mutation of the MYBPC3 (c.1504 C>T p.Arg502 Trp) probably underlie the disease.