Recessive DES cardio/myopathy without myofibrillar aggregates: intronic splice variant silences one allele leaving only missense L190P-desmin.

ABSTRACT: We establish autosomal recessive DES variants p.(Leu190Pro) and a deep intronic splice variant causing inclusion of a frameshift-inducing artificial exon/intronic fragment, as the likely cause of myopathy with cardiac involvement in female siblings. Both sisters presented in their twenties with slowly progressive limb girdle weakness, severe systolic dysfunction, and progressive, severe respiratory weakness. Desmin is an intermediate filament protein typically associated with autosomal dominant myofibrillar myopathy with cardiac involvement. However a few rare cases of autosomal recessive desminopathy are reported. In this family, a paternal missense p.(Leu190Pro) variant was viewed unlikely to be causative of autosomal dominant desminopathy, as the father and brothers carrying this varian

SUBMITTER: Riley LG 

PROVIDER: S-EPMC6777463 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature