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Whole Exome Sequencing Reveals Novel and Recurrent Disease-Causing Variants in Lens Specific Gap Junctional Protein Encoding Genes Causing Congenital Cataract

Berry, Vanita; Ionides, Alex; Pontikos, Nikolas; Moghul, Ismail; Moore, Anthony T.; Quinlan, Roy A.; Michaelides, Michel

Whole Exome Sequencing Reveals Novel and Recurrent Disease-Causing Variants in Lens Specific Gap Junctional Protein Encoding Genes Causing Congenital Cataract Thumbnail


Authors

Vanita Berry

Alex Ionides

Nikolas Pontikos

Ismail Moghul

Anthony T. Moore

Michel Michaelides



Abstract

Pediatric cataract is clinically and genetically heterogeneous, and is the most common cause of childhood blindness worldwide. In this study, we aimed to identify disease-causing variants in three large British families and one isolated case with autosomal dominant congenital cataract, using whole exome sequencing. We identified four different heterozygous variants, three in the large families and one in the isolated case. Family A, with a novel missense variant (c.178G>C, p.Gly60Arg) in GJA8 with lamellar cataract; family B, with a recurrent variant in GJA8 (c.262C>T, p.Pro88Ser) associated with nuclear cataract; and family C, with a novel variant in GJA3 (c.771dupC, p.Ser258GlnfsTer68) causing a lamellar phenotype. Individual D had a novel variant in GJA3 (c.82G>T, p.Val28Leu) associated with congenital cataract. Each sequence variant was found to cosegregate with disease. Here, we report three novel and one recurrent disease-causing sequence variant in the gap junctional protein encoding genes causing autosomal dominant congenital cataract. Our study further extends the mutation spectrum of these genes and further facilitates clinical diagnosis. A recurrent p.P88S variant in GJA8 causing isolated nuclear cataract provides evidence of further phenotypic heterogeneity associated with this variant.

Citation

Berry, V., Ionides, A., Pontikos, N., Moghul, I., Moore, A. T., Quinlan, R. A., & Michaelides, M. (2020). Whole Exome Sequencing Reveals Novel and Recurrent Disease-Causing Variants in Lens Specific Gap Junctional Protein Encoding Genes Causing Congenital Cataract. Genes, 11(5), Article 512. https://doi.org/10.3390/genes11050512

Journal Article Type Article
Acceptance Date May 4, 2020
Online Publication Date May 6, 2020
Publication Date May 31, 2020
Deposit Date May 5, 2020
Publicly Available Date May 14, 2020
Journal Genes
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 11
Issue 5
Article Number 512
DOI https://doi.org/10.3390/genes11050512

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Advance online version This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.







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