Kristiina Avela1, Riitta Salonen-Kajander2, Arja Laitinen3, Simon Ramsden4, Stephanie Barton4, Sirkka-Liisa Rudanko5,6. 1. The Department of Clinical Genetics, Helsinki University Hospital, HUSLAB, Helsinki, Finland. 2. Norio Centre, Rinnekoti Foundation, Helsinki, Finland. 3. The Department of Ophthalmology, Helsinki University Hospital, Helsinki, Finland. 4. St Mary's Hospital, Central Manchester University Hospitals and Manchester Centre for Genomic Medicine, Manchester, UK. 5. Visio Low Vision Research Centre, Finnish Federation of the Visually Impaired, Helsinki, Finland. 6. Finnish Register of Visual Impairment by National Institute for Health and Welfare, Helsinki, Finland.
Abstract
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.
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.
Authors: Manon H C A Peeters; Mubeen Khan; Anoek A M B Rooijakkers; Timo Mulders; Lonneke Haer-Wigman; Camiel J F Boon; Caroline C W Klaver; L Ingeborgh van den Born; Carel B Hoyng; Frans P M Cremers; Anneke I den Hollander; Claire-Marie Dhaenens; Rob W J Collin Journal: Hum Mutat Date: 2021-09-20 Impact factor: 4.700
Authors: Nikolas Pontikos; Gavin Arno; Neringa Jurkute; Elena Schiff; Rola Ba-Abbad; Samantha Malka; Ainoa Gimenez; Michalis Georgiou; Genevieve Wright; Monica Armengol; Hannah Knight; Menachem Katz; Mariya Moosajee; Patrick Yu-Wai-Man; Anthony T Moore; Michel Michaelides; Andrew R Webster; Omar A Mahroo Journal: Ophthalmology Date: 2020-04-16 Impact factor: 12.079