Key result
Exome sequencing identifies novel DES and known MYH7 variants in familial restrictive cardiomyopathy.
Why the study?
Restrictive cardiomyopathy has a heterogeneous genetic basis, and identifying molecular causes is important for diagnosis and family screening.
Case Report (n=1)
No
The identification of a novel DES variant and a MYH7 variant in a familial restrictive cardiomyopathy case expands the genetic spectrum of the disease, highlighting candidates for future functional validation.
Cautious clinical interpretation required pending validation; leaves open the variants' role in familial restrictive cardiomyopathy.
Background Restrictive cardiomyopathy (RCM) is a rare, severe cardiac disease with a heterogeneous genetic basis. Both genetic and nongenetic factors contribute to RCM pathogenesis. Identifying the underlying molecular causes is important for diagnosis and family screening. In this study, we investigated the genetic basis of RCM in a 52‐year‐old woman with a family history of RCM and heart disease. Methods Genetic predisposition was evaluated using whole‐exome sequencing (WES). Candidate variants identified in the proband were validated by Sanger sequencing and interpreted using bioinformatics tools and the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. Results Two heterozygous missense variants were identified: a novel DES c.262C > A (p.Leu88Met) variant and a previously reported MYH7 c.2360G > A (p.Arg787His) variant. The DES variant was absent from population databases and was classified as a variant of uncertain significance, whereas the MYH7 variant has been reported in the cardiomyopathy spectrum, primarily in hypertrophic cardiomyopathy. Although both variants may be relevant to the participant’s phenotype, their contribution remains uncertain without segregation and functional studies. Conclusion These findings expand the spectrum of DES and MYH7 variants observed in cardiomyopathy and highlight the need for further segregation and functional analyses to clarify their clinical significance in RCM. Identifying the genetic basis of RCM in this family may improve screening strategies and guide clinical management.
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Moghaddam et al. (2026) conducted a case report in Familial Restrictive Cardiomyopathy (RCM) (n=1). Whole-exome sequencing (WES) was evaluated on Identification of genetic variants associated with familial restrictive cardiomyopathy. Whole-exome sequencing identified a novel DES p.Leu88Met variant and a previously reported MYH7 p.Arg787His variant in a 52-year-old woman with familial restrictive cardiomyopathy.
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