Comprehensive functional testing in fibroblasts has strong utility to diagnose mitochondrial disease

ABSTRACT: Genome sequencing is the first-line diagnostic method for primary mitochondrial diseases (PMDs), yet its effectiveness is limited by variants of uncertain significance or unresolved genetic findings. We systematically evaluated the clinical performance of fibroblast-based functional testing, comprised of respiratory chain enzyme assays, blue native polyacrylamide gel electrophoresis with in-gel activity staining (BN-PAGE), complex I assembly analysis, and targeted protein abundance assessments, in a cohort of 204 genetically confirmed PMD patients, 51 healthy controls, and 53 patients with differential diagnoses. Individually, enzyme assays, BN-PAGE, and complex I assembly analysis showed sensitivities of 46%, 40%, and 49%, with specificities of 93, 98 and 99%, respectively. Combined, the

SUBMITTER: Johan, L.K. Van Hove 

PROVIDER: S-SCDT-10_1038-S44321-026-00497-3 | biostudies-other |

REPOSITORIES: biostudies-other