Bi-allelic variants in COQ8B, a gene involved in the biosynthesis of coenzyme Q10, lead to non-syndromic retinitis pigmentosa
Year: 2024
Type: article
Abstract: Retinitis pigmentosa (RP) is a Mendelian disease characterized by gradual loss of vision, due to the progressive degeneration of retinal cells. Genetically, it is highly heterogeneous, with pathogenic variants identified in more than 100 genes so far. Following a large-scale sequencing screening, we identified five individuals (four families) with recessive and non-syndromic RP, carrying as well bi-allelic DNA changes in COQ8B, a gene involved in the biosynthesis of coenzyme Q10. Specifically, we detected compound heterozygous assortments of five disease-causing variants (c.187C>T [p.Arg63Trp], c.566G>A [p.Trp189Ter], c.1156G>A [p.Asp386Asn], c.1324G>A [p.Val442Met], and c.1560G>A [p.Trp520Ter]), all segregating with disease according to a recessive pattern of inheritance. Cell-based analysis of recombinant proteins deriving from these genotypes, performed by target engagement assays, showed in all cases a significant decrease in ligand-protein interaction compared to the wild type. Our results indicate that variants in COQ8B lead to recessive non-syndromic RP, possibly by impairing the biosynthesis of coenzyme Q10, a key component of oxidative phosphorylation in the mitochondria.
Authors: Ana Belén Iglesias-Romero, Karolina Kaminska, Mathieu Quinodoz, Marc Folcher, Siying Lin, Gavin Arno, Joaquim Calado, Andrew R. Webster, Alexandre Moulin, Ana Berta Sousa, Luisa Coutinho-Santos, Cristina Santos, Carlo Rivolta
Institutions: University of Basel, Institute of Molecular and Clinical Ophthalmology Basel, University of Leicester, NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital, University College London, Moorfields Eye Hospital NHS Foundation Trust, Greenwood Genetic Center, Universidade Nova de Lisboa, Fondation Asile des Aveugles, University of Lausanne, University of Lisbon, Centro Hospitalar Lisboa Norte, Instituto de Oftalmologia Dr Gama Pinto
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,150
Funders: National Science Foundation, Wellcome Trust, Heart of England NHS Foundation Trust, Cancer Research UK, National Institute for Health and Care Research, Department of Health and Social Care, Fight for Sight UK, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Moorfields Eye Hospital NHS Foundation Trust, Moorfields Eye Charity, Medical Research Council, UCL Institute of Ophthalmology, University College London
OpenAlex ID: W4402128042