Riga East Clinical University Hospital Riga Latvia
Eissa Faqeih
Section of Medical Genetics Children's Specialist Hospital, King Fahad Medical City Riyadh Saudi Arabia
Namik Kaya
Translational Genomics Department MBC: 26, Centre for Genomic Medicine Riyadh Saudi Arabia
Zita Krumina
Department of Biology and Microbiology Riga Stradiņš University Riga Latvia
Johannes A. Mayr
University Children’s Hospital, Laboratory Salzburger Landeskliniken Universitaetsklinikum of the Paracelsus Medical University Salzburg Salzburg Austria
Ieva Micule
Department of Medical Genetics and Prenatal Diagnostics Children's University Hospital Riga Latvia
Nathan Thompson Wright
Department of Chemistry and Biochemistry James Madison University Harrisonburg Virginia USA
Melanie T. Achleitner
University Children’s Hospital, Laboratory Salzburger Landeskliniken Universitaetsklinikum of the Paracelsus Medical University Salzburg Salzburg Austria
Hanan AlQudairy
Translational Genomics Department MBC: 26, Centre for Genomic Medicine Riyadh Saudi Arabia
Sander Pajusalu
Department of Clinical Genetics, Genetics and Personalized Medicine Clinic Tartu University Hospital Tartu Estonia
Janis Stavusis
Latvian Biomedical Research and Study Centre Riga Latvia
Pawel Zayakin
Latvian Biomedical Research and Study Centre Riga Latvia
Inna Inashkina
Latvian Biomedical Research and Study Centre Riga Latvia
Abstract The PTCD3 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 PTCD3 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 (p A, p.(Tyr394Ter) and c.805C>T, p.(His269Tyr). Tyr394Ter variant ablates the C‐terminal half of the protein, including a significant portion of the central fold. In silico modelling for the variant His269Tyr shows that the inclusion of the slightly larger tyrosine sidechain is well tolerated, with no significant change in either the position or the movement of the surrounding area. The third case is a 9‐year‐old boy, who has a global developmental delay, central hypotonia, hyperreflexia and abnormal MRI. PTCD3 pathogenic variant c.538+4A>G was identified by whole exome sequencing. To test the variant's effect on splicing, an RT‐PCR experiment was performed, which revealed skipping of an out‐of‐frame exon 7.
