High throughput genetic screening of 51 paediatric cataract genes identifies causative mutations in inherited paediatric cataract in South Eastern Australia
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Date
2017-08-24
Authors
Javadiyan, Shahrbanou
Craig, Jamie E
Souzeau, Emmanuelle
Sharma, Shiwani
Lower, Karen Marie
Mackey, David A
Staffieri, Sandra E
Elder, James E
Taranath, Deepa A
Straga, Tania
Journal Title
Journal ISSN
Volume Title
Publisher
Genetics Society of America.
Rights
Copyright © 2017 Javadiyan et al.
Rights Holder
Javadiyan et al.
Abstract
Paediatric cataract is a leading cause of childhood blindness. This study aimed to determine the genetic cause of paediatric cataract in Australian families by screening known disease associated genes using massively parallel sequencing technology. We sequenced 51 previously reported paediatric cataract genes in 33 affected individuals with a family history (cases with previously known or published mutations were excluded) using the Ion Torrent Personal Genome Machine. Variants were prioritised for validation if they were predicted to alter the protein sequence and were absent or rare with minor allele frequency <1% in public databases. Confirmed mutations were assessed for segregation with the phenotype in all available family members. All identified novel or previously reported cataract causing mutations were screened in 326 unrelated Australian controls. We detected eleven novel mutations in GJA3, GJA8, CRYAA, CRYBB2, CRYGS, CRYGA, GCNT2, CRYGA and MIP, three previously reported cataract causing mutations in GJA8, CRYAA and CRYBB2. The most commonly mutated genes were those coding for gap junctions and crystallin proteins. Including previous reports of paediatric cataract associated mutations in our Australian cohort, known genes account for more than 60 % of familial paediatric cataract in Australia, indicating that still more causative genes remain to be identified.
Description
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords
Ion torrent, PGM, ongenital cataract, paediatric cataract, massively parallel sequencing
Citation
Javadiyan, S., Craig, J. E., Souzeau, E., Sharma, S., Lower, K. M., Mackey, D. A., ... & Black, J. (2017). High Throughput Genetic Screening of 51 Paediatric Cataract Genes Identifies Causative Mutations in Inherited Paediatric Cataract in South Eastern Australia. G3: Genes, Genomes, Genetics, g3-300109.