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MIR204 n.37C>T variant as a cause of chorioretinal dystrophy variably associated with iris coloboma,early-onset cataracts and congenital glaucoma |
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| Authors: | Jana Jedlickova Marie Vajter Tomas Barta Graeme C. M. Black Rahat Perveen Jan Mares Marek Fichtl Bohdan Kousal Lubica Dudakova Petra Liskova |
| Affiliation: | 1. Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic;2. Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic;3. Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic;4. Division of Evolution, and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK;5. Division of Evolution, and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK;6. Department of Ophthalmology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic |
| Abstract: | Four members of a three-generation Czech family with early-onset chorioretinal dystrophy were shown to be heterozygous carriers of the n.37C>T in MIR204. The identification of this previously reported pathogenic variant confirms the existence of a distinct clinical entity caused by a sequence change in MIR204. Chorioretinal dystrophy was variably associated with iris coloboma, congenital glaucoma, and premature cataracts extending the phenotypic range of the condition. In silico analysis of the n.37C>T variant revealed 713 novel targets. Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants. Haplotype analysis excluded relatedness with the original family reported to harbour the n.37C>T variant in MIR204. Identification of a second independent family confirms the existence of a distinct MIR204-associated clinical entity and suggests that the phenotype may also involve congenital glaucoma. |
| Keywords: | albinism chorioretinal dystrophy coloboma congenital glaucoma MIR204 OCA2 premature cataract |