EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden
Autor: | Monica Holmberg, Lennart Österman, Irina Golovleva, Frida Jonsson, Ida Maria Westin, Marie Burstedt |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male Retinal Pigment Epithelium Cohort Studies 0302 clinical medicine Sanger sequencing Genetics Aged 80 and over Multidisciplinary Middle Aged Founder Effect symbols Medicine Female Medical Genetics Retinitis Pigmentosa Adult Genetic counseling RNA Splicing Science Genes Recessive Biology Article 03 medical and health sciences symbols.namesake Young Adult Medical research Retinitis pigmentosa medicine Humans Multiplex ligation-dependent probe amplification Eye Proteins Gene Alleles Aged Medicinsk genetik Sweden Genetic heterogeneity medicine.disease Exon skipping Ophthalmology 030104 developmental biology HEK293 Cells Mutation 030221 ophthalmology & optometry Oftalmologi Minigene |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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 the second most common genetic cause of RP in northern Sweden accounting for at least 18%. 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. |
Databáze: | OpenAIRE |
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