@article{discovery10053448, note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.}, year = {2018}, month = {June}, volume = {32}, pages = {1661--1668}, journal = {Eye}, title = {Whole-genome sequencing reveals a recurrent missense mutation in the Connexin 46 (GJA3) gene causing autosomal-dominant lamellar cataract}, issn = {1476-5454}, author = {Berry, V and Ionides, ACW and Pontikos, N and Moghul, I and Moore, AT and Cheetham, ME and Michaelides, M}, url = {http://dx.doi.org/10.1038/s41433-018-0154-8}, 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.7āGā{\ensuremath{>}}āT; 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.} }