Desmin common mutation is associated with multi-systemic disease manifestations and depletion of mitochondria and mitochondrial DNA

摘要: Desmin (DES) is a major muscle scaffolding protein that also functions to anchor mitochondria. Pathogenic DES mutations, however, have not previously been recognized as cause of multi-systemic mitochondrial disease. Here, we describe 45-year-old man who presented The Children’s Hospital Philadelphia Mitochondrial-Genetics Diagnostic Clinic for evaluation progressive cardiac, neuromuscular, gastrointestinal, and mood disorders. Muscle biopsy at age 45 was remarkable cytoplasmic bodies, well ragged red fibers SDH positive/COX negative were suggestive myopathy. showed significant reductions in content (16% control mean citrate synthase activity) DNA (35% mean). His family history cardiac conduction defects myopathy multiple maternal relatives. Multiple single gene panel-based sequencing studies unrevealing. Whole exome identified known pathogenic p.S13F mutation had associated with desmin-related Desmin-related an autosomal dominant disorder characterized by right ventricular hypertrophic cardiomyopathy, myopathy, arrhythmias. However, neuropathy, gastrointestinal dysfunction, depletion both mitochondria widely this disorder. Recognition dysfunction occurs clarifies the basis manifestations, are typical primary Understanding pathophysiology highlights possibility new therapies otherwise untreatable often fatal class We postulate drug treatments aimed improving biogenesis or reducing oxidative stress may be effective ameliorate effects