Bi-allelic variants in COQ8B, a gene involved in the biosynthesis of coenzyme Q10, lead to non-syndromic retinitis pigmentosa.
Am J Hum Genet
; 111(10): 2299-2306, 2024 Oct 03.
Article
em En
| MEDLINE
| ID: mdl-39226897
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.
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MEDLINE
Assunto principal:
Linhagem
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Retinose Pigmentar
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Ubiquinona
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Alelos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article