Key result
Next-generation sequencing identified novel compound heterozygous MYBPC3 mutations in a 12-year-old boy with hypertrophic cardiomyopathy, whose LVOT pressure gradient improved to 21 mm Hg after 3 months of metoprolol.
Why the study?
Analyses of gene mutations associated with HCM are valuable for molecular diagnosis, genetic counseling, and management of familial HCM.
Case Report (n=1)
No
Next-generation sequencing successfully identified novel compound heterozygous mutations in the MYBPC3 gene in a 12-year-old boy with severe hypertrophic cardiomyopathy, whose LVOT obstruction improved with metoprolol therapy.
Supports genetic testing in pediatric HCM; leaves open pathogenicity and management implications of MYBPC3 truncations.
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.
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Chen et al. (2019) conducted a case report in Hypertrophic cardiomyopathy (n=1). Next-generation sequencing (NGS) and Metoprolol was evaluated on Identification of pathogenic mutations and reduction in LVOT pressure gradient. Next-generation sequencing identified novel compound heterozygous MYBPC3 mutations in a 12-year-old boy with hypertrophic cardiomyopathy, whose LVOT pressure gradient improved to 21 mm Hg after 3 months of metoprolol.
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