biostudies-literatureUnknownSmith TBIntramural NIH HHSRNIDNIDCD NIH HHSWellcome TrustThe mitoribosome synthesizes 13 protein subunits of the oxidative phosphorylation system encoded by the mitochondrial genome. The mitoribosome is composed of 12S rRNA, 16S rRNA and 82 mitoribosomal proteins encoded by nuclear genes. To date, variants in 12 genes encoding mitoribosomal proteins are associated with rare monogenic disorders, and frequently show combined oxidative phosphorylation deficiency. Here, we describe five unrelated individuals with biallelic variants in the <i>DAP3</i> nuclear gene encoding mitoribosomal small subunit 29 (MRPS29), with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. Assessment of respiratory chain function and proteomic profiling of fimedRxiv : the preprint server for health sciences2024.08.19.24312079https://www.ebi.ac.uk/biostudies/studies/S-EPMC11451657biostudies-literatureBiallelic variants in &lt;i&gt;DAP3&lt;/i&gt; result in reduced assembly of the mitoribosomal small subunit with altered intrinsic and extrinsic apoptosis and a Perrault syndrome-spectrum phenotype.PMC11451657097820/Z/11/BS35T32 DC000039Z01 DC000039203105/Z/16/ZSmith TBDDD StudyConway GSOlahova MCarrera SThompson KYue WWElmaleh-Berges MO' Sullivan JProkisch HBarzik MFriedman TBJahic ABen Chehida AEllingford JMRadhakrishnan PBanka SDemain LAMYeole MBelyantseva IAWilliams SGMunro KJJoss SBhaskar SSJenkinson EMHoulden HGlasgow RICSchiff MShukla ANewman WGHe LBeetz CUrquhart JEKopajtich RTaylor RWThomas HBO'Keefe RTAzzouz HRea ABlakes AJMfalseBiallelic variants in &lt;i&gt;DAP3&lt;/i&gt; result in reduced assembly of the mitoribosomal small subunit with altered intrinsic and extrinsic apoptosis and a Perrault syndrome-spectrum phenotype.The mitoribosome synthesizes 13 protein subunits of the oxidative phosphorylation system encoded by the mitochondrial genome. The mitoribosome is composed of 12S rRNA, 16S rRNA and 82 mitoribosomal proteins encoded by nuclear genes. To date, variants in 12 genes encoding mitoribosomal proteins are associated with rare monogenic disorders, and frequently show combined oxidative phosphorylation deficiency. Here, we describe five unrelated individuals with biallelic variants in the <i>DAP3</i> nuclear gene encoding mitoribosomal small subunit 29 (MRPS29), with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. Assessment of respiratory chain function and proteomic profiling of fi2024-01-01T00:00:00Z2024 Aug2026-04-08T18:59:32.635Z2025-04-04T09:58:22.785ZS-EPMC114516573937113110.1101/2024.08.19.24312079