Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases.

ABSTRACT: Variants in the mitochondrial genome (mtDNA) cause a diverse collection of mitochondrial diseases and have extensive phenotypic overlap with Mendelian diseases encoded on the nuclear genome. The mtDNA is not always specifically evaluated in patients with suspected Mendelian disease, resulting in overlooked diagnostic variants. Here, we analyzed a cohort of 6,660 rare disease families (5,625 genetically undiagnosed [84%]) from the Genomics Research to Elucidate the Genetics of Rare diseases (GREGoR) Consortium, as well as other rare disease cohorts. Using dedicated pipelines to address the technical challenges posed by the mtDNA-circular genome, variant heteroplasmy, and nuclear misalignment-we called single nucleotide variants, small insertions/deletions, and large mtDNA deletions from exo

SUBMITTER: Stenton SL 

PROVIDER: S-EPMC12278631 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature