心脏肌钙蛋白I-R145W突变所致肥厚型心肌病表型特点分析

Analyzation of Phenotype of Hypertrophic Cardiomyopathy Associated With R145W Mutation in Cardiac Troponin I.

目的明确心脏肌钙蛋白I(cTnI)R145W突变的表型特点。方法在300例肥厚型心肌病(HCM)患者及120例正常对照中对心脏肌钙蛋白I基因(TNNI3)外显子7进行基因扫描,聚合酶链反应(PCR)扩增目的片段,双脱氧末段终止法测序。对R145W突变患者进行家系调查,收集临床资料,分析其临床表型。结果在4个先证者家系9个HCM成员中发现cTnI-R145W突变,2/3的患者表现为心尖部肥厚,3/4先证者有猝死家族史,其中一例家族成员在随访期内心源性猝死。结论 cTnI-R145W突变可导致心尖部肥厚为主的HCM,其表型恶性程度较高。结合同一突变位点在西方人群中可以导致典型的限制型心肌病表型,提示R145W可以导致不同类型的心肌病。

Ob ject ive To describe the phenotype of hypertrophic cardiomyopathy(HCM) associated with R145W mutation in gene encoding cardiac troponin I (TNNI3). Meth ods A systematic mutation screening of exon 7 of TNNI3 gene was performed in 300 unrelated Chinese adult patients with HCM and 120 controls using di rect DNA sequencing, and then the phenotype associated with R145Wwas analyzed. Resu lts R145W mutat ion was identi��ed in 4 index patients with HCM. Nine patients in the four pedigrees weremade a de��nite diagnosis ofHCM by echocardiography and carried the R145Wmutation. Two thirds of the 9 HCM patients expressed apical cardiac hypertropgy. Three quarters of the 4 index HCM patients had a familial history of sudden cardic death. Conclu sion An apical cardiac hypertrophy and poor prognos is were possibly associated with R145W mutation in TNNI3. Taking account of the samemutat ion identi��ed in restrict ive cardiomyopathy (RCM) patients in western populat ion, R145W mutat ion in TNNI3 might create distinct phenotype of cardiomyopathy.