Relationships of MYH7 and TNNI3 mutations with familial hypertrophic cardiomyopathy

CHEN Pei; YAN Jifeng

doi:10.3969/j.issn.1002-266X.2017.32.008

Abstract：Objective To observe the gene mutation types in a Chinese Han hypertrophic cardiomyopathy (HCM) family and to explore its effect on clinical phenotype.Methods We selected 1 Chinese Han HCM family, including 13 family members, among whom 5 were diagnosed as HCM.New generation of high-throughput sequencing technology (NGS) was used to sequence the 44 genes of the target genomes associated with human cardiomyopathy of the proband.The results indicated that the proband carried β-myosin heavy chain (MYH7) gene Arg663His in exon 18 and troponin I (TNNI3) gene c.470C>T in exon 7.The mutations of the two genes in other members of the family were detected by the dideoxy chain-termination method, and the clinical manifestations of HCM patients with MYH7 and TNNI3 gene mutations were analyzed.Results The proband and his sister carried MYH7 gene exon 18 Arg663His mutation and TNNI3 gene exon 7 c.470C> T mutation, and the age of onset was respectively 2 and 1 years old.The ECG showed abnormal Q wave, ST-T changes, and left ventricular high voltage.Echocardiography showed left atrium enlargement, the thickest part of interventricular septum was 25 and 23 mm, SAM was positive, and the left ventricular outflow pressure were 80 and 68 mmHg, respectively.The proband''s mother, uncle and grandfather carried Arg663His mutation in MYH7 gene exon 18, and the age of onset was 21, 19, and 30 years old, respectively.The ECG showed ST-T changes and left ventricular high voltage.Echocardiography showed that the thickest part of interventricular septum were 16, 18, and 18 mm, respectively, SAM were negative, and no left ventricular outflow tract obstruction.The proband′s cousin only carried Arg663His mutation in MYH7 gene exon 18.There were no obvious clinical symptoms, and no abnormalities in ECG and echocardiogram.Conclusions The TNNI3 gene in the HCM family underwent de novo mutation, and the MYH7 gene mutation was inherited.The patients with double mutations of MYH7 and TNNI3 gene presented a younger onset age, severe clinical phenotype and poor prognosis.