A case of retinitis pigmentosa homozygous for a rare CNGA1 causal variant

Abstract Retinitis pigmentosa (RP) is a heterogenous hereditary disorder leading to blindness. Despite using next-generation sequencing technologies, causal variants in about 60% of RP cases remain unknown. The heterogeneous genetic inheritance pattern makes it difficult to pinpoint causal variants....

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Autores principales:	Kohei Saito, Norimoto Gotoh, Inyeop Kang, Toshio Shimada, Takeshi Usui, Chikashi Terao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3f1269759009437093811c6307872aa5
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spelling	oai:doaj.org-article:3f1269759009437093811c6307872aa52021-12-02T13:30:11ZA case of retinitis pigmentosa homozygous for a rare CNGA1 causal variant10.1038/s41598-021-84098-92045-2322https://doaj.org/article/3f1269759009437093811c6307872aa52021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84098-9https://doaj.org/toc/2045-2322Abstract Retinitis pigmentosa (RP) is a heterogenous hereditary disorder leading to blindness. Despite using next-generation sequencing technologies, causal variants in about 60% of RP cases remain unknown. The heterogeneous genetic inheritance pattern makes it difficult to pinpoint causal variants. Besides, rare penetrating variants are hardly observed in general case–control studies. Thus, a family-based analysis, specifically in a consanguineous family, is a clinically and genetically valuable approach for RP. We analyzed a Japanese consanguineous family with a member suffering from RP with a typical autosomal recessive pattern. We sequenced five direct descendants and spouse using Whole-exome sequencing (WES) and Whole-genome sequencing (WGS). We identified a homozygous pathogenic missense variant in CNGA1 (NM_000087.3, c.839G > A, p.Arg280His) in the proband, while we found no homozygous genotypes in the other family members. CNGA1 was previously reported to be associated with RP. We confirmed the genotypes by the Sanger sequencing. Additionally, we assessed the homozygous genotype in the proband for the possibility of a founder mutation using homozygosity analysis. Our results suggested the two copies of the variant derived from a founder mutation. In conclusion, we found the homozygotes for c.839G > A in CNGA1 as causal for RP.Kohei SaitoNorimoto GotohInyeop KangToshio ShimadaTakeshi UsuiChikashi TeraoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kohei Saito Norimoto Gotoh Inyeop Kang Toshio Shimada Takeshi Usui Chikashi Terao A case of retinitis pigmentosa homozygous for a rare CNGA1 causal variant
description	Abstract Retinitis pigmentosa (RP) is a heterogenous hereditary disorder leading to blindness. Despite using next-generation sequencing technologies, causal variants in about 60% of RP cases remain unknown. The heterogeneous genetic inheritance pattern makes it difficult to pinpoint causal variants. Besides, rare penetrating variants are hardly observed in general case–control studies. Thus, a family-based analysis, specifically in a consanguineous family, is a clinically and genetically valuable approach for RP. We analyzed a Japanese consanguineous family with a member suffering from RP with a typical autosomal recessive pattern. We sequenced five direct descendants and spouse using Whole-exome sequencing (WES) and Whole-genome sequencing (WGS). We identified a homozygous pathogenic missense variant in CNGA1 (NM_000087.3, c.839G > A, p.Arg280His) in the proband, while we found no homozygous genotypes in the other family members. CNGA1 was previously reported to be associated with RP. We confirmed the genotypes by the Sanger sequencing. Additionally, we assessed the homozygous genotype in the proband for the possibility of a founder mutation using homozygosity analysis. Our results suggested the two copies of the variant derived from a founder mutation. In conclusion, we found the homozygotes for c.839G > A in CNGA1 as causal for RP.
format	article
author	Kohei Saito Norimoto Gotoh Inyeop Kang Toshio Shimada Takeshi Usui Chikashi Terao
author_facet	Kohei Saito Norimoto Gotoh Inyeop Kang Toshio Shimada Takeshi Usui Chikashi Terao
author_sort	Kohei Saito
title	A case of retinitis pigmentosa homozygous for a rare CNGA1 causal variant
title_short	A case of retinitis pigmentosa homozygous for a rare CNGA1 causal variant
title_full	A case of retinitis pigmentosa homozygous for a rare CNGA1 causal variant
title_fullStr	A case of retinitis pigmentosa homozygous for a rare CNGA1 causal variant
title_full_unstemmed	A case of retinitis pigmentosa homozygous for a rare CNGA1 causal variant
title_sort	case of retinitis pigmentosa homozygous for a rare cnga1 causal variant
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3f1269759009437093811c6307872aa5
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A case of retinitis pigmentosa homozygous for a rare CNGA1 causal variant

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