High-throughput genetic screening of 51 pediatric cataract genes identifies causative mutations in inherited pediatric cataract in South Eastern Australia

Shari Javadiyan, Jamie E. Craig, Emmanuelle Souzeau, Shiwani Sharma, Karen M. Lower, David A. Mackey, Sandra E. Staffieri, James E. Elder, Deepa Taranath, Tania Straga, Joanna Black, John Pater, Theresa Casey, Alex W. Hewitt, Kathryn P. Burdon

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Pediatric cataract is a leading cause of childhood blindness. This study aimed to determine the genetic cause of pediatric cataract in Australian families by screening known disease-associated genes using massively parallel sequencing technology. We sequenced 51 previously reported pediatric 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 prioritized 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 11 novel mutations in GJA3, GJA8, CRYAA, CRYBB2, CRYGS, CRYGA, GCNT2, CRYGA, and MIP; and 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 pediatric cataract-associated mutations in our Australian cohort, known genes account for .60% of familial pediatric cataract in Australia, indicating that still more causative genes remain to be identified.

Original languageEnglish
Pages (from-to)3257-3268
Number of pages12
JournalG3: Genes, Genomes, Genetics
Volume7
Issue number10
DOIs
Publication statusPublished - 1 Oct 2017

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South Australia
Genetic Testing
Cataract
Pediatrics
Mutation
Genes
High-Throughput Nucleotide Sequencing
Crystallins
Connexins
Blindness
Gene Frequency
Genome
Databases
Ions
Technology
Phenotype

Cite this

Javadiyan, Shari ; Craig, Jamie E. ; Souzeau, Emmanuelle ; Sharma, Shiwani ; Lower, Karen M. ; Mackey, David A. ; Staffieri, Sandra E. ; Elder, James E. ; Taranath, Deepa ; Straga, Tania ; Black, Joanna ; Pater, John ; Casey, Theresa ; Hewitt, Alex W. ; Burdon, Kathryn P. / High-throughput genetic screening of 51 pediatric cataract genes identifies causative mutations in inherited pediatric cataract in South Eastern Australia. In: G3: Genes, Genomes, Genetics. 2017 ; Vol. 7, No. 10. pp. 3257-3268.
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abstract = "Pediatric cataract is a leading cause of childhood blindness. This study aimed to determine the genetic cause of pediatric cataract in Australian families by screening known disease-associated genes using massively parallel sequencing technology. We sequenced 51 previously reported pediatric 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 prioritized 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 11 novel mutations in GJA3, GJA8, CRYAA, CRYBB2, CRYGS, CRYGA, GCNT2, CRYGA, and MIP; and 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 pediatric cataract-associated mutations in our Australian cohort, known genes account for .60{\%} of familial pediatric cataract in Australia, indicating that still more causative genes remain to be identified.",
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Javadiyan, S, Craig, JE, Souzeau, E, Sharma, S, Lower, KM, Mackey, DA, Staffieri, SE, Elder, JE, Taranath, D, Straga, T, Black, J, Pater, J, Casey, T, Hewitt, AW & Burdon, KP 2017, 'High-throughput genetic screening of 51 pediatric cataract genes identifies causative mutations in inherited pediatric cataract in South Eastern Australia' G3: Genes, Genomes, Genetics, vol. 7, no. 10, pp. 3257-3268. https://doi.org/10.1534/g3.117.300109

High-throughput genetic screening of 51 pediatric cataract genes identifies causative mutations in inherited pediatric cataract in South Eastern Australia. / Javadiyan, Shari; Craig, Jamie E.; Souzeau, Emmanuelle; Sharma, Shiwani; Lower, Karen M.; Mackey, David A.; Staffieri, Sandra E.; Elder, James E.; Taranath, Deepa; Straga, Tania; Black, Joanna; Pater, John; Casey, Theresa; Hewitt, Alex W.; Burdon, Kathryn P.

In: G3: Genes, Genomes, Genetics, Vol. 7, No. 10, 01.10.2017, p. 3257-3268.

Research output: Contribution to journalArticle

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T1 - High-throughput genetic screening of 51 pediatric cataract genes identifies causative mutations in inherited pediatric cataract in South Eastern Australia

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AU - Craig, Jamie E.

AU - Souzeau, Emmanuelle

AU - Sharma, Shiwani

AU - Lower, Karen M.

AU - Mackey, David A.

AU - Staffieri, Sandra E.

AU - Elder, James E.

AU - Taranath, Deepa

AU - Straga, Tania

AU - Black, Joanna

AU - Pater, John

AU - Casey, Theresa

AU - Hewitt, Alex W.

AU - Burdon, Kathryn P.

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KW - Cataract

KW - Congenital

KW - Ion Torrent

KW - Massively parallel

KW - Mutant Screen

KW - Pediatric cataract

KW - PGM

KW - Report

KW - Sequencing

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