Vanita Berry1, Alexander C W Ionides2, Nikolas Pontikos3,4, Ismail Moghul5, Anthony T Moore2,6, Michael E Cheetham3, Michel Michaelides7,8. 1. UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK. v.berry@ucl.ac.uk. 2. Moorfields Eye Hospital, London, EC1V 2PD, UK. 3. UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK. 4. UCL Genetics Institute, University College London, London, WC1E 6BT, UK. 5. UCL Cancer Institute, University College London, London, WC1E 6DD, UK. 6. Ophthalmology Department, University of California School of Medicine, San Francisco, CA, 94158, USA. 7. UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK. michel.michaelides@ucl.ac.uk. 8. Moorfields Eye Hospital, London, EC1V 2PD, UK. michel.michaelides@ucl.ac.uk.
Abstract
PURPOSE: Congenital cataract, opacification of the ocular lens, is clinically and genetically a heterogeneous childhood disease. In this study we aimed to identify the underlying genetic cause of isolated autosomal-dominant lamellar cataract in a multi-generation English family. METHODS: Whole-genome sequencing (WGS) was undertaken in two affected subjects and one unaffected individual. Segregation analysis was performed and a known cataract-causing mutation was identified. Segregation was further validated by sanger sequencing in the entire pedigree. RESULTS: A heterozygous mutation c.7 G > T; p.D3Y was identified in an NH2-terminal region of the gap junction protein GJA3 and found to co-segregate with disease. CONCLUSION: We have identified a recurrent mutation in GJA3 in a large British pedigree causing the novel phenotype of autosomal-dominant congenital lamellar cataract. Previously, p.D3Y was found in a Hispanic family causing pulverulent cataract. WGS proved an efficient method to find the underlying molecular cause in this large family, which could not be mapped due to uninformative markers.
PURPOSE:Congenital cataract, opacification of the ocular lens, is clinically and genetically a heterogeneous childhood disease. In this study we aimed to identify the underlying genetic cause of isolated autosomal-dominant lamellar cataract in a multi-generation English family. METHODS: Whole-genome sequencing (WGS) was undertaken in two affected subjects and one unaffected individual. Segregation analysis was performed and a known cataract-causing mutation was identified. Segregation was further validated by sanger sequencing in the entire pedigree. RESULTS: A heterozygous mutation c.7 G > T; p.D3Y was identified in an NH2-terminal region of the gap junction protein GJA3 and found to co-segregate with disease. CONCLUSION: We have identified a recurrent mutation in GJA3 in a large British pedigree causing the novel phenotype of autosomal-dominant congenital lamellar cataract. Previously, p.D3Y was found in a Hispanic family causing pulverulent cataract. WGS proved an efficient method to find the underlying molecular cause in this large family, which could not be mapped due to uninformative markers.
Authors: H M Berman; J Westbrook; Z Feng; G Gilliland; T N Bhat; H Weissig; I N Shindyalov; P E Bourne Journal: Nucleic Acids Res Date: 2000-01-01 Impact factor: 16.971
Authors: Jun-Jie Tong; Peter J Minogue; Matthew Kobeszko; Eric C Beyer; Viviana M Berthoud; Lisa Ebihara Journal: J Membr Biol Date: 2014-11-18 Impact factor: 1.843