Biallelic variants in coenzyme Q10 biosynthesis pathway genes cause a retinitis pigmentosa phenotype

Jurkute, Neringa, Cancellieri, Francesca, Pohl, Lisa, Li, Catherina HZ, Heaton, Robert A, Reurink, Janine, Bellingham, James, Quinodoz, Mathieu, Yioti, Georgia, Stefaniotou, Maria
et al (show 14 more authors) (2022) Biallelic variants in coenzyme Q10 biosynthesis pathway genes cause a retinitis pigmentosa phenotype. NPJ GENOMIC MEDICINE, 7 (1). 60-.

Access the full-text of this item by clicking on the Open Access link.


The aim of this study was to investigate coenzyme Q10 (CoQ<sub>10</sub>) 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<sub>10</sub> 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<sub>10</sub> 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<sub>10</sub> 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.

Item Type: Article
Uncontrolled Keywords: Genomics England Research Consortium
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 07 Feb 2023 09:43
Last Modified: 07 Feb 2023 09:43
DOI: 10.1038/s41525-022-00330-z
Open Access URL:
Related URLs: