Next-generation sequencing (NGS) as a molecular diagnostic tool for hypertrophic cardiomyopathy in a Chinese boy due to novel compound heterozygous mutations in the MYBPC3 gene

Abstract

Rationale: Hypertrophic cardiomyopathy (HCM) is mainly caused by mutations in genes encoding sarcomeric proteins. One of the most commonly mutated HCM genes is the MYBPC3 gene. Mutations in this gene lead mainly to truncation of the protein, which gives rise to a relatively severe phenotype. Analyses of gene mutations associated with HCM are valuable for molecular diagnosis, genetic counseling, and management of familial HCM. Patient concerns: A 12-year-old boy presented with palpitations and dyspnea after exercise for 1 year. Echocardiography showed myocardial asymmetric hypertrophy of the ventricular septum, the anterior wall, and the lateral wall of the left ventricle. The thickness of the interventricular septum was estimated to be 33 mm. ECG showed left ventricular high voltage and ST-T changes. He had been diagnosed with HCM 3 months previously. Diagnoses: Due to his clinical presentation, he was determined to have HCM via a molecular analysis, revealing compound heterozygotes (p.R597W and p.Q1012Sfs∗8) in the MYBPC3 gene. Interventions: The patient was prescribed metoprolol to slow the heart rate and increase diastolic filling time. Outcomes: The boy was treated with metoprolol 6.75 mg b.i.d. Approximately 3 months later, review of the echocardiography showed that the peak velocity across the LVOT dropped to 2.3 m/seconds and that the pressure gradient dropped to 21 mm Hg. Lessons: A custom next-generation sequencing (NGS) technology for the HCM panel allowed us to identify compound heterozygous mutations in the MYBPC3 gene, confirming NGS as a molecular diagnostic tool.

Novel pathogenic variant of MYBPC3 responsible for hypertrophic cardiomyopathy

“…However, nonsense variants are rarely reported in Chinese families with hypertrophic cardiomyopathy. 14,15 Elucidating the clinical characteristics of hypertrophic cardiomyopathy caused by MYBPC3 variations is of great significance for accurately judging the prognosis and stratifying the risk of hypertrophic cardiomyopathy. In this study, comprehensive screening of pathogenic genes was carried out in a Han Chinese family with hypertrophic cardiomyopathy.…”