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Biallelic variants in coenzyme Q10 biosynthesis pathway genes cause a retinitis pigmentosa phenotype.
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4694922
Author(s) Jurkute, Neringa; Cancellieri, Francesca; Pohl, Lisa; Li, Catherina H Z; Heaton, Robert A; Reurink, Janine; Bellingham, James; Quinodoz, Mathieu; Yioti, Georgia; Stefaniotou, Maria; Weener, Marianna; Zuleger, Theresia; Haack, Tobias B; Stingl, Katarina; Genomics England Research Consortium, ; Hoyng, Carel B; Mahroo, Omar A; Hargreaves, Iain; Raymond, F Lucy; Michaelides, Michel; Rivolta, Carlo; Kohl, Susanne; Roosing, Susanne; Webster, Andrew R; Arno, Gavin
Author(s) at UniBasel Rivolta, Carlo
Year 2022
Title Biallelic variants in coenzyme Q10 biosynthesis pathway genes cause a retinitis pigmentosa phenotype.
Journal NPJ genomic medicine
Volume 7
Number 1
Pages / Article-Number 60
Abstract

The aim of this study was to investigate coenzyme Q10 (CoQ; 10; ) biosynthesis pathway defects in inherited retinal dystrophy. Individuals affected by inherited retinal dystrophy (IRD) underwent exome or genome sequencing for molecular diagnosis of their condition. Following negative IRD gene panel analysis, patients carrying biallelic variants in CoQ; 10; biosynthesis pathway genes were identified. Clinical data were collected from the medical records. Haplotypes harbouring the same missense variant were characterised from family genome sequencing (GS) data and direct Sanger sequencing. Candidate splice variants were characterised using Oxford Nanopore Technologies single molecule sequencing. The CoQ; 10; status of the human plasma was determined in some of the study patients. 13 individuals from 12 unrelated families harboured candidate pathogenic genotypes in the genes: PDSS1, COQ2, COQ4 and COQ5. The PDSS1 variant c.589 A > G was identified in three affected individuals from three unrelated families on a possible ancestral haplotype. Three variants (PDSS1 c.468-25 A > G, PDSS1 c.722-2 A > G, COQ5 c.682-7 T > G) were shown to lead to cryptic splicing. 6 affected individuals were diagnosed with non-syndromic retinitis pigmentosa and 7 had additional clinical findings. This study provides evidence of CoQ; 10; biosynthesis pathway gene defects leading to non-syndromic retinitis pigmentosa in some cases. Intronic variants outside of the canonical splice-sites represent an important cause of disease. RT-PCR nanopore sequencing is effective in characterising these splice defects.

Publisher Springer Nature Limited
ISSN/ISBN 2056-7944
Full Text on edoc
Digital Object Identifier DOI 10.1038/s41525-022-00330-z
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/36266294
   


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