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Published on: August 8, 2022
A novel cardiac myosin-binding protein C S297X mutation in hypertrophic cardiomyopathy
Takayoshi Hirota1, Toru Kubo, Hiroaki Kitaoka
1Department of Medicine and Geriatrics, Kochi Medical School, Oko-cho, Nankoku-shi, Kochi 783-8505, Japan.
Insights
A novel MYBPC3 gene mutation, S297X, causes hypertrophic cardiomyopathy (HCM) across a wide age range. Clinical manifestations are diverse, but the condition appears to have a generally benign prognosis.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Genetic Heart Diseases
Background:
- Mutations in the cardiac myosin-binding protein C gene (MYBPC3) are linked to hypertrophic cardiomyopathy (HCM).
- MYBPC3-associated HCM often presents with delayed onset and a favorable prognosis.
Purpose of the Study:
- To investigate clinical features of familial HCM caused by a new nonsense mutation, S297X, in the MYBPC3 gene.
- Evaluate the phenotypic spectrum associated with the S297X MYBPC3 mutation.
Main Methods:
- Genetic analysis of sarcomere protein genes in 93 hypertrophic cardiomyopathy (HCM) probands.
- Clinical evaluation and follow-up of patients identified with the S297X MYBPC3 mutation.
Main Results:
- The S297X MYBPC3 nonsense mutation was identified in nine individuals from two families.
- Eight of nine mutation carriers were phenotype-positive, with diagnoses ranging from 9 to 75 years.
- Observed left ventricular hypertrophy (LVH) patterns were diverse, with some patients showing outflow tract obstruction; most remained clinically stable.
Conclusions:
- The novel S297X MYBPC3 mutation is a cause of hypertrophic cardiomyopathy (HCM) with variable age of onset and diverse clinical presentations.
- Despite heterogeneous manifestations, the clinical course for patients with the S297X MYBPC3 mutation appears to be benign.
Background:
Mutations in the cardiac myosin-binding protein C gene (MYBPC3) have been reported to be associated with delayed expression of hypertrophic cardiomyopathy (HCM) and a relatively good prognosis.
Purpose:
The aim of this study was to evaluate clinical manifestations in patients with familial HCM caused by a novel nonsense mutation, S297X, in MYBPC3.
Methods:
We analyzed the sarcomere protein genes in 93 probands with HCM.
Results:
The nonsense mutation S297X in MYBPC3 was present in nine subjects from two unrelated families. Eight of those nine subjects with this mutation were found to be phenotype-positive and the remaining individual was not affected phenotypically. The age range at diagnosis was 9-75 years. There was no family history of sudden death in either family. At presentation, there were various left ventricular hypertrophy (LVH) patterns, including Maron type III hypertrophy from the LV base to apex, hypertrophy confined to the anterolateral wall at the basal LV wall. Two patients showed a significant LV outflow tract gradient and one patient showed intra-right-ventricular obstruction. During follow-up, one patient was repeatedly hospitalized for the treatment of heart failure after development of paroxysmal atrial fibrillation at the age of 86 years and the remaining eight subjects were in relatively stable condition and did not require hospitalization for the treatment of HCM-related events.
Conclusion:
The novel mutation S297X in MYBPC3 causes HCM in a broad range of ages and heterogeneous clinical manifestations, though the clinical course in patients with this mutation seems to be benign.
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