Biallelic variants in <i>MRPL49</i> cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency.

ABSTRACT: Combined oxidative phosphorylation deficiency (COXPD) is a rare multisystem disorder which is clinically and genetically heterogeneous. Genome sequencing identified biallelic MRPL49 variants in individuals from five unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly and retinal dystrophy. Complexome profiling of fibroblasts from affected individuals revealed reduced levels of the small and, a more pronounced reduction of, the large mitochondrial ribosomal subunits. There was no evidence of altered mitoribosomal assembly. The reductions in levels of OXPHOS enzyme complexes I and IV are consistent with a form of COXPD associate

SUBMITTER: Thomas HB 

PROVIDER: S-EPMC11483032 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature