| 余东阳,高建步,李雨雷,等.TTN基因新发突变致家族性扩张型心肌病一家系的临床表型与基因检测分析[J].安徽医药,2026,30(4):745-748. |
| TTN基因新发突变致家族性扩张型心肌病一家系的临床表型与基因检测分析 |
| Clinical phenotype and genetic analysis of a familial dilated cardiomyopathy pedigree caused by a novel TTN gene mutation |
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| DOI：10.3969/j.issn.1009-6469.2026.04.021 |
| 中文关键词: 心肌病，扩张型 肌联蛋白 基因组突变 全外显子组高通量测序 遗传学 |
| 英文关键词: Cardiomyopathy,dilated Titin Genomic mutation Whole exome sequencing Genetics |
| 基金项目:国家重点研发计划项目( 2018YFC1312400)；河南省科技攻关联合共建项目( LHGJ20221049) |
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| 中文摘要: |
| 目的通过对一个家族性扩张型心肌病(DCM)家系成员进行临床表型和基因检测结果的分析，研究其 DCM相关基因突变及其可能的致病机制，并为家系成员的 DCM预防与个性化诊治提供科学依据。方法在 2023年 4月至 2024年 10月所纳入的一个家族性 DCM家系中，收集 4名成员(包括 2例 DCM病人)的临床病历和基因检测结果。对比 DCM病人在诊治前后的临床表型变化，明确其临床特点；通过对病人的全外显子组高通量测序(WES)筛选与 DCM相关的候选基因突变位点，结合权威数据库及生物信息学工具预测突变的致病性；对健康成员进行 Sanger测序，探究突变在家系成员中的分布情况，进行家系共分离分析，共同分析突变与临床的相关性。结果在该家系中， DCM病人经规范治疗后心功能改善显著； 2例病人和 1名健康成员的肌联蛋白(TTN)基因在染色体 chr2:178614293位置存在 c.44181T>A的突变，均为杂合状态，而另 1名健康成员未发现该突变。该突变为新发错义突变，在人群基因组突变频率数据库(gnomAD)等数据库中未见收录。生物信息学分析表明，该突变显著影响肌联蛋白功能，可能与 DCM的发病机制相关。结合家系共分离分析，初步判定该突变为可能致病突变。结论该研究通过对一个家族性 DCM家系的遗传学研究，发现并验证了 TTN基因中一个全新的、可能致病的突变位点(c.44181T>A)。该发现不仅为该家系成员的 DCM预防与精准诊治提供了科学依据，还为进一步研究 TTN突变在 DCM中的致病机制提供了重要线索。 |
| 英文摘要: |
| Objective To investigate the mutations in DCM-related genes and their potential pathogenic mechanisms by analyzingthe clinical phenotypes and genetic testing results of members in a familial dilated cardiomyopathy (DCM) pedigree, and to provide ascientific basis for the prevention and personalized diagnosis and treatment of DCM in family members.Methods From April 2023 toOctober 2024, clinical data and genetic testing results were collected from four members of a family with familial DCM, including twoaffected individuals. The clinical phenotype changes of DCM patients before and after diagnosis and treatment were compared to eluci-date their clinical characteristics. Whole exome sequencing (WES) was employed to screen for candidate gene mutation sites associatedwith DCM. The pathogenicity of identified mutations was predicted using authoritative databases and bioinformatics tools. Sanger se-quencing was performed on healthy family members to explore the distribution of mutations within the pedigree, followed by co-segrega-tion analysis to assess the correlation between mutations and clinical phenotypes.Results In this pedigree, DCM patients exhibitedsignificant improvement in cardiac function following standardized treatment. Both patients and one healthy family member harbored aheterozygous c.44181T>A mutation in the titin (TTN) gene at chromosome chr2:178614293, whereas the other healthy member did notcarry this mutation. This novel missense mutation was not recorded in population databases such as gnomAD. Bioinformatics analysisresults indicated that the mutation significantly impacted titin function, potentially contributing to the pathogenesis of DCM. Combinedwith co-segregation analysis, the mutation was preliminarily classified as potentially pathogenic.Conclusions This genetic study of afamilial DCM pedigree identified and validated a novel, potentially pathogenic mutation site (c.44181T>A) in the TTN gene. This dis-covery not only provides a scientific basis for the prevention and precise treatment of DCM in family members but also offers important insights for further research into the pathogenic mechanisms of TTN mutations in DCM. |
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