biostudies-literatureLace BEesti TeadusagentuurKing Salman Center for Disability ResearchNational Institutes of HealthNational Science BoardEuropean Regional Development Fund297-304https://www.ebi.ac.uk/biostudies/studies/S-EPMC11558465biostudies-literatureUnknown65(5)The <i>PTCD3</i> gene product (protein PTCD3 or MRPS39) forms the entry channel of the mitochondrial small ribosomal subunit and binds to single-stranded mRNA. Here, we expand on the clinical manifestations of <i>PTCD3</i> pathogenic variants by describing an early-onset patient with Leigh-like syndrome and two patients with milder form of disease, with combined oxidative phosphorylation deficiency. A 34-year-old male and his 33-year-old sister both have horizontal nystagmus, pronounced rough tremor, truncal ataxia, dysmetria, spasticity and hyperreflexia. The basal respiration rate decreased significantly for the male patient and his mother (<i>p</i> < 0.0001) compared to the controls. The whole genome sequencing analysis revealed two heterozygous variants in the <i>PTCD3</i>: c.1182T>A, JIMD reportsThe phenotypic spectrum of <i>PTCD3</i> deficiency.PMC11558465R15GM148890PSG774MCB‐2024182KSRG‐2022‐105KSCDR‐RAC: 2180 0041.1.1.1/18/A/096Kaya NWright NTMayr JAMicule ILace BFaqeih EKrumina ZAchleitner MTPajusalu SStavusis JAlQudairy HZayakin PInashkina IfalseThe phenotypic spectrum of <i>PTCD3</i> deficiency.The <i>PTCD3</i> gene product (protein PTCD3 or MRPS39) forms the entry channel of the mitochondrial small ribosomal subunit and binds to single-stranded mRNA. Here, we expand on the clinical manifestations of <i>PTCD3</i> pathogenic variants by describing an early-onset patient with Leigh-like syndrome and two patients with milder form of disease, with combined oxidative phosphorylation deficiency. A 34-year-old male and his 33-year-old sister both have horizontal nystagmus, pronounced rough tremor, truncal ataxia, dysmetria, spasticity and hyperreflexia. The basal respiration rate decreased significantly for the male patient and his mother (<i>p</i> < 0.0001) compared to the controls. The whole genome sequencing analysis revealed two heterozygous variants in the <i>PTCD3</i>: c.1182T>A, 2024-01-01T00:00:00Z2024 Sep2026-06-02T10:38:59.272Z2025-04-04T00:21:59.106ZS-EPMC115584653954468810.1002/jmd2.12424