Mutations in the gene may lead to restrictive phenotype hypertrophic cardiomyopathy with poor prognosis: case report.

BACKGROUND

Genetic disorders are a significant cause of cardiomyopathies. Mutations in the gene (OMIM #604488) encoding the Z-disc protein Telethonin associated with a mixed phenotype of hypertrophic and restrictive cardiomyopathy with poor prognosis have not yet been reported.

CASE SUMMARY

A 47-year-old male presented with heart failure symptoms over a year, which had worsened in the past week. He has a familial history of cardiomyopathy, as his mother was diagnosed with restrictive cardiomyopathy (RCM). Transthoracic echocardiography and cardiac magnetic resonance imaging (CMR) revealed non-obstructive hypertrophic cardiomyopathy (HCM) with severe diastolic dysfunction, biatrial enlargement, preserved ejection fraction, and normal chamber size. Endomyocardial biopsy demonstrated cardiomyocyte hypertrophy and focal fibrosis. The patient was diagnosed with hypertrophic cardiomyopathy with a restrictive phenotype (RP-HCM). Whole exome sequencing identified a frameshift mutation producing a truncated product (p.Glu12fs) in the family. Despite interventions, the patient's cardiac function progressively deteriorated, leading to his placement on the heart transplant waiting list 1 year later.

DISCUSSION

In conclusion, we report for the first time that a heterozygous frameshift mutation resulting in a truncated protein product may contribute to the development of RP-HCM, providing new insights into the genetic basis of cardiomyopathy with mixed phenotypes.