Abstract
BackgroundVariants in the desmin gene (DES) are associated with desminopathy; a myofibrillar myopathy mainly characterized by muscle weakness, conduction block, and dilated cardiomyopathy. To date, only ~50 disease-associated variants have been described, and the majority of these lead to dominant-negative effects. However, the complete genotypic spectrum of desminopathy is not well established.Case presentationNext-generation sequencing was performed on 51 cardiac disease genes in a proband with profound skeletal myopathy, dilated cardiomyopathy, and respiratory dysfunction. Our analyses revealed compound heterozygous DES variants, both of which are predicted to lead to a loss-of-function. Consistent with recessive inheritance, each variant was identified in an unaffected parent.ConclusionsThis case report serves to broaden the variant spectrum of desminopathies and provides insight into the molecular mechanisms of desminopathy, supporting distinct dominant-negative and loss-of-function etiologies.
Highlights
Variants in the desmin gene (DES) are associated with desminopathy; a myofibrillar myopathy mainly characterized by muscle weakness, conduction block, and dilated cardiomyopathy
This case report serves to broaden the variant spectrum of desminopathies and provides insight into the molecular mechanisms of desminopathy, supporting distinct dominant-negative and loss-of-function etiologies
Sequence analysis of 51 cardiomyopathy genes revealed two heterozygous variants in the DES gene: c.600delG which is predicted to result in a frameshift and subsequent premature termination codon
Summary
Variants in the desmin gene (DES) are associated with desminopathy; a myofibrillar myopathy mainly characterized by muscle weakness, conduction block, and dilated cardiomyopathy. Desminopathies are myofibrillar myopathies mainly characterized by progressive muscle weakness, conduction block, dilated cardiomyopathy, and in severe cases, sudden death. The overwhelming majority of diseaseassociated DES variants described far are missense variants inherited in a dominant fashion These variants commonly result in a dominant-negative effect on wildtype proteins, leading to destabilization of desmin intermediate filament networks, accumulation of mutant desmin aggregates, and myofibrillar disorganization and. Case presentation The proband (Figure 1A; III-1, arrow), was the full term product of a pregnancy complicated by a reportedly prolonged period in the birth canal Following vaginal delivery, she was noted to have a hemorrhage in the back of the brain which affected swallowing. The patient received Botox injections for tight heel cords at age 14 and reportedly became nonambulatory shortly thereafter
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call