{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T19:24:12Z","timestamp":1793733852794,"version":"4.6.1"},"posted":{"date-parts":[[2024,10,11]]},"group-title":"Genetic and Genomic Medicine","reference-count":37,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,10,11]]},"abstract":"<jats:p>\n                  Combined oxidative phosphorylation deficiency (COXPD) is a rare multisystem disorder which is clinically and genetically heterogeneous. Genome sequencing identified biallelic\n                  <jats:italic>MRPL49<\/jats:italic>\n                  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 associated with biallelic\n                  <jats:italic>MRPL49<\/jats:italic>\n                  variants, expanding the understanding of how disruption of the mitochondrial ribosomal large subunit results in multi-system phenotypes.\n                <\/jats:p>","DOI":"10.1101\/2024.10.10.24315152","type":"posted-content","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T13:40:19Z","timestamp":1728654019000},"source":"Crossref","is-referenced-by-count":3,"title":["Biallelic variants in\n                  <i>MRPL49<\/i>\n                  cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9626-9706","authenticated-orcid":false,"given":"Huw 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