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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ftdoajarticles:oai:doaj.org/article:7d1c0a553203498cb63fcaadea9dd10e 2023-05-15T17:44:23+02:00 EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden Ida Maria Westin Frida Jonsson Lennart Österman Monica Holmberg Marie Burstedt Irina Golovleva 2021-04-01T00:00:00Z https://doi.org/10.1038/s41598-021-87224-9 https://doaj.org/article/7d1c0a553203498cb63fcaadea9dd10e EN eng Nature Portfolio https://doi.org/10.1038/s41598-021-87224-9 https://doaj.org/toc/2045-2322 doi:10.1038/s41598-021-87224-9 2045-2322 https://doaj.org/article/7d1c0a553203498cb63fcaadea9dd10e Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) Medicine R Science Q article 2021 ftdoajarticles https://doi.org/10.1038/s41598-021-87224-9 2022-12-31T07:12:46Z 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. Article in Journal/Newspaper Northern Sweden Directory of Open Access Journals: DOAJ Articles Scientific Reports 11 1 |
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Directory of Open Access Journals: DOAJ Articles |
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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 |
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Medicine R Science Q |
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 in Journal/Newspaper |
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://doi.org/10.1038/s41598-021-87224-9 https://doaj.org/article/7d1c0a553203498cb63fcaadea9dd10e |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_source |
Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
op_relation |
https://doi.org/10.1038/s41598-021-87224-9 https://doaj.org/toc/2045-2322 doi:10.1038/s41598-021-87224-9 2045-2322 https://doaj.org/article/7d1c0a553203498cb63fcaadea9dd10e |
op_doi |
https://doi.org/10.1038/s41598-021-87224-9 |
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Scientific Reports |
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11 |
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1766146607716237312 |