The genetic aetiology of retinal degeneration in children in Finland – new founder mutations identified
| Autor: | Sirkka-Liisa Rudanko, Riitta Salonen-Kajander, Simon C Ramsden, Kristiina Avela, Arja Laitinen, Stephanie Barton |
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| Přispěvatelé: | Clinicum, Department of Medical and Clinical Genetics, HUSLAB, Department of Ophthalmology and Otorhinolaryngology, Silmäklinikka, HUS Head and Neck Center |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Retinal degeneration Adolescent DNA Mutational Analysis Population FOUNDER MUTATION visual impairment Retinoschisis Biology PHENOTYPE 03 medical and health sciences 0302 clinical medicine Retinitis pigmentosa RETINITIS-PIGMENTOSA TULP1 Electroretinography medicine Humans Genetic Predisposition to Disease 3125 Otorhinolaryngology ophthalmology Child Eye Proteins education Gene Finland Genetics education.field_of_study Genetic heterogeneity Incidence Retinal Degeneration RETINOSCHISIS Dystrophy General Medicine medicine.disease Pedigree 3. Good health PREVALENCE Ophthalmoscopy molecular genetic aetiology Ophthalmology Child Preschool Mutation BLINDNESS 030221 ophthalmology & optometry Etiology Next-generation sequencing paediatric retinal degeneration Female 030217 neurology & neurosurgery |
| Popis: | Purpose To study the genetic aetiology and phenotypes of retinal degeneration (RD) in Finnish children born during 1993-2009. Methods Children with retinal degeneration (N = 68) were investigated during 2012-2014 with a targeted gene analysis or a next-generation sequencing (NGS) based gene panel. Also, a full clinical ophthalmological examination was performed. Results The cohort covered 44% (68/153) of the Finnish children with inherited RD born 1993-2009. X-linked retinoschisis, retinitis pigmentosa, Leber congenital amaurosis and cone-rod dystrophy were the most common clinical diagnoses in the study group. Pathogenic mutations were found in 17 retinal genes. The molecular genetic aetiology was identified in 77% of the patients (in 77% of the families) analysed by NGS method. Several founder mutations were detected including three novel founder mutations c.148delG in TULP1, c.2314C>R (p.Gln772Ter) in RPGRIP1 and c.533G>A (Trp178Ter) in TYR. We also confirmed the previous tentative finding of c.2944 + 1delG in GYCU2D being the most frequent cause of Leber congenital amaurosis (LCA) in Finland. Conclusions Globally, RD is genetically heterogeneous with over 260 disease genes reported so far. This was shown not to be the case in Finland, where the genetic aetiology of RD is caused by a small group of genes, due to several founder mutations that are enriched in the population. We found that X-chromosomal retinoschisis constitutes the major group in Finnish paediatric RD population and is almost exclusively caused by two founder mutations. Several other founder mutations were detected including three novel founder mutations. All in all, the genetic aetiology of 77% of families was identified which is higher than previously reported from other populations, likely due to the specific genomic constitution of the Finns. |
| Databáze: | OpenAIRE |
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