EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden

Abstract Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of inherited retinal degenerations. The ortholog of Drosophila eyes shut/spacemaker, EYS on chromosome 6q12 is a major genetic cause of recessive RP worldwide, with prevalence of 5 to 30%. In this study, by using...

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Autores principales:	Ida Maria Westin, Frida Jonsson, Lennart Österman, Monica Holmberg, Marie Burstedt, Irina Golovleva
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7d1c0a553203498cb63fcaadea9dd10e
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spelling	oai:doaj.org-article:7d1c0a553203498cb63fcaadea9dd10e2021-12-02T14:17:16ZEYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden10.1038/s41598-021-87224-92045-2322https://doaj.org/article/7d1c0a553203498cb63fcaadea9dd10e2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87224-9https://doaj.org/toc/2045-2322Abstract Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of inherited retinal degenerations. The ortholog of Drosophila eyes shut/spacemaker, EYS on chromosome 6q12 is a major genetic cause of recessive RP worldwide, with prevalence of 5 to 30%. In this study, by using targeted NGS, MLPA and Sanger sequencing we uncovered the EYS gene as one of the most common genetic cause of autosomal recessive RP in northern Sweden accounting for at least 16%. The most frequent pathogenic variant was c.8648_8655del that in some patients was identified in cis with c.1155T>A, indicating Finnish ancestry. We also showed that two novel EYS variants, c.2992_2992+6delinsTG and c.3877+1G>A caused exon skipping in human embryonic kidney cells, HEK293T and in retinal pigment epithelium cells, ARPE-19 demonstrating that in vitro minigene assay is a straightforward tool for the analysis of intronic variants. We conclude, that whenever it is possible, functional testing is of great value for classification of intronic EYS variants and the following molecular testing of family members, their genetic counselling, and inclusion of RP patients to future treatment studies.Ida Maria WestinFrida JonssonLennart ÖstermanMonica HolmbergMarie BurstedtIrina GolovlevaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ida Maria Westin Frida Jonsson Lennart Österman Monica Holmberg Marie Burstedt Irina Golovleva EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden
description	Abstract Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of inherited retinal degenerations. The ortholog of Drosophila eyes shut/spacemaker, EYS on chromosome 6q12 is a major genetic cause of recessive RP worldwide, with prevalence of 5 to 30%. In this study, by using targeted NGS, MLPA and Sanger sequencing we uncovered the EYS gene as one of the most common genetic cause of autosomal recessive RP in northern Sweden accounting for at least 16%. The most frequent pathogenic variant was c.8648_8655del that in some patients was identified in cis with c.1155T>A, indicating Finnish ancestry. We also showed that two novel EYS variants, c.2992_2992+6delinsTG and c.3877+1G>A caused exon skipping in human embryonic kidney cells, HEK293T and in retinal pigment epithelium cells, ARPE-19 demonstrating that in vitro minigene assay is a straightforward tool for the analysis of intronic variants. We conclude, that whenever it is possible, functional testing is of great value for classification of intronic EYS variants and the following molecular testing of family members, their genetic counselling, and inclusion of RP patients to future treatment studies.
format	article
author	Ida Maria Westin Frida Jonsson Lennart Österman Monica Holmberg Marie Burstedt Irina Golovleva
author_facet	Ida Maria Westin Frida Jonsson Lennart Österman Monica Holmberg Marie Burstedt Irina Golovleva
author_sort	Ida Maria Westin
title	EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden
title_short	EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden
title_full	EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden
title_fullStr	EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden
title_full_unstemmed	EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden
title_sort	eys mutations and implementation of minigene assay for variant classification in eys-associated retinitis pigmentosa in northern sweden
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7d1c0a553203498cb63fcaadea9dd10e
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EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden

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