Exome sequencing identifies novel and recurrent mutations in GJA8 and CRYGD associated with inherited cataract

Donna S. Mackay, Thomas M. Bennett, Susan M. Culican, Alan Shiels

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Background: Inherited cataract is a clinically important and genetically heterogeneous cause of visual impairment. Typically, it presents at an early age with or without other ocular/systemic signs and lacks clear phenotype-genotype correlation rendering both clinical classification and molecular diagnosis challenging. Here we have utilized trio-based whole exome sequencing to discover mutations in candidate genes underlying autosomal dominant cataract segregating in three nuclear families. Results: In family A, we identified a recurrent heterozygous mutation in exon-2 of the gene encoding γD-crystallin (CRYGD; c.70C > A, p.Pro24Thr) that co-segregated with 'coralliform' lens opacities. Families B and C were found to harbor different novel variants in exon-2 of the gene coding for gap-junction protein α8 (GJA8; c.20T > C, p.Leu7Pro and c.293A > C, p.His98Pro). Each novel variant co-segregated with disease and was predicted in silico to have damaging effects on protein function. Conclusions: Exome sequencing facilitates concurrent mutation-profiling of the burgeoning list of candidate genes for inherited cataract, and the results can provide enhanced clinical diagnosis and genetic counseling for affected families.

Original languageEnglish (US)
Article number8
JournalHuman Genomics
Volume8
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Bibliographical note

Funding Information:
We thank the families for their participation in this study and the Genome Technology Access Center (GTAC) at Washington University School of Medicine for help with genomic analysis. GTAC is partially supported by National Institutes of Health (NIH) grants P30 CA91842 and UL1 TR000448. This work was supported by NIH grants EY012284 (to A.S.) and EY02687 (Core Grant for Vision Research) and by an unrestricted grant to the Department of Ophthalmology and Visual Sciences from Research to Prevent Blindness (RPB).

Funding Information:
We thank the families for their participation in this study and the Genome Technology Access Center (GTAC) at Washington University School of Medicine for help with genomic analysis. GTAC is partially supported by National Institutes of Health (NIH) grants P30 CA91842 and UL1 TR000448. This work was supported by NIH grants EY012284 (to A.S.) and EY02687

Publisher Copyright:
© 2014 Mackay et al.

Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.

Keywords

  • CRYGD
  • Cataract
  • Exome sequencing
  • GJA8

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