Related Experiment Video
Updated: Aug 16, 2025
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Bi-Allelic DES Gene Variants Causing Autosomal Recessive Myofibrillar Myopathies Affecting Both Skeletal Muscles and
Maria Elena Onore1, Marco Savarese2,3, Esther Picillo1
1Medical Genetics and Cardiomyology, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Napoli, Italy.
Insights
Autosomal recessive desminopathies, caused by desmin gene mutations, are rare and severe. This study details a case of a fatal recessive desminopathy, highlighting its progressive nature and genetic basis.
Area of Science:
- Genetics
- Cardiology
- Neurology
Background:
- Mutations in the human desmin gene (DES) are linked to cardiomyopathies and myopathies.
- Autosomal dominant desminopathies manifest as cardiac conduction disorders and myopathy.
- Autosomal recessive desminopathies are rare, with variable phenotypes and potential for early sudden cardiac death.
Observation:
- A case of autosomal recessive desminopathy in an Italian boy with consanguineous parents is presented.
- The patient developed progressive myopathy at age 12 and dilated cardiomyopathy at age 16.
- He died at age 17 from intractable heart failure.
Findings:
- Next Generation Sequencing (NGS) identified a homozygous loss-of-function variant (c.634C>T; p.Arg212*) in the DES gene.
- This variant was likely inherited from both consanguineous parents.
- Clinical and genetic data were compared with previously reported cases.
Implications:
- This case expands the understanding of autosomal recessive desminopathies and their severe cardiac manifestations.
- Highlights the importance of genetic testing in diagnosing rare myopathies with cardiac involvement.
- Further research into genotype-phenotype correlations in desminopathies is warranted.
Abstract:
Mutations in the human desmin gene (DES) may cause both autosomal dominant and recessive cardiomyopathies leading to heart failure, arrhythmias and atrio-ventricular blocks, or progressive myopathies. Cardiac conduction disorders, arrhythmias and cardiomyopathies usually associated with progressive myopathy are the main manifestations of autosomal dominant desminopathies, due to mono-allelic pathogenic variants. The recessive forms, due to bi-allelic variants, are very rare and exhibit variable phenotypes in which premature sudden cardiac death could also occur in the first or second decade of life. We describe a further case of autosomal recessive desminopathy in an Italian boy born of consanguineous parents, who developed progressive myopathy at age 12, and dilated cardiomyopathy four years later and died of intractable heart failure at age 17. Next Generation Sequencing (NGS) analysis identified the homozygous loss-of-function variant c.634C>T; p.Arg212*, which was likely inherited from both parents. Furthermore, we performed a comparison of clinical and genetic results observed in our patient with those of cases so far reported in the literature.
More Related Videos
Related Concept Videos
01:43Sex-linked Disorders
01:05Desmosomes
01:35Pedigree Analysis
01:21Satellite Stem Cells and Muscular Dystrophy
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:11Genetic Lingo