A founder mutation inCERKLis a major cause of retinal dystrophy in Finland
| Autor: | Kristiina Avela, Kristiina Aittomäki, Stephanie Barton, Liina Kuuluvainen, Sanna Seitsonen, Eeva-Marja Sankila, Stuart Gillies |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Adolescent DNA Mutational Analysis Mutation Missense Visual Acuity ABCA4 Receptors Cell Surface Compound heterozygosity Bioinformatics medicine.disease_cause Retina Cohort Studies 03 medical and health sciences 0302 clinical medicine CERKL Gene Retinal Dystrophies Electroretinography medicine Humans Missense mutation Child Eye Proteins Exome Finland Aged Genetics Mutation biology High-Throughput Nucleotide Sequencing General Medicine Middle Aged Founder Effect Pedigree 3. Good health Phosphotransferases (Alcohol Group Acceptor) Ophthalmology 030104 developmental biology Guanylate Cyclase 030221 ophthalmology & optometry biology.protein GUCY2D ATP-Binding Cassette Transporters Female Visual Fields Microtubule-Associated Proteins Founder effect |
| Zdroj: | Acta Ophthalmologica. 96:183-191 |
| ISSN: | 1755-375X |
| Popis: | Purpose To study the genetic aetiology of retinal dystrophies (RD) in Finnish patients. Methods A targeted next-generation sequencing (NGS) panel of 105 retinal dystrophy genes was used in a cohort of 55 RD patients. Results The overall diagnostic yield was 60% demonstrating the power of this approach. Interestingly, a missense mutation c.375C>G p.(Cys125Trp) in the CERKL gene was found in 18% of the patients in either a homozygous or compound heterozygous state. Data from Exome Aggregation Consortium (ExAC) Browser show that the CERKL c.375C>G p.(Cys125Trp) allele is enriched in the Finnish population and thus is a founder mutation. Furthermore, we report the clinical picture of 18 patients with mutations in the CERKL gene. CERKL mutations cause a macular-onset disease, in which symptoms first become apparent at the second decade. We also detected other novel founder mutations in the CERKL, EYS, RP1, ABCA4 and GUCY2D genes. Conclusion Our report indicates that the first diagnostic test for Finnish patients with sporadic or autosomal recessive RD should be a targeted test for founder mutations in the CERKL, EYS, RP1, ABCA4 and GUCY2D genes. These results confirm the utility of NGS-based gene panels as a powerful method for mutation identification in RD, thus enabling improved genetic counselling for these families. |
| Databáze: | OpenAIRE |
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