Pathogenic genetic variants identified in Australian families with paediatric cataract

Johanna L. Jones, Bennet J. McComish, Sandra E. Staffieri, Emmanuelle Souzeau, Lisa S. Kearns, James E. Elder, Jac C. Charlesworth, David A. Mackey, Jonathan B. Ruddle, Deepa Taranath, John Pater, Theresa Casey, Jamie E. Craig, Kathryn P. Burdon

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Objective: Paediatric (childhood or congenital) cataract is an opacification of the normally clear lens of the eye and has a genetic basis in at least 18% of cases in Australia. This study aimed to replicate clinical gene screening to identify variants likely to be causative of disease in an Australian patient cohort. 

Methods and analysis: Sixty-three reported isolated cataract genes were screened for rare coding variants in 37 Australian families using genome sequencing.

Results: Disease-causing variants were confirmed in eight families with variant classification as â € likely pathogenic'. This included novel variants PITX3 p.(Ter303LeuextTer100), BFSP1 p.(Glu375GlyfsTer2), and GJA8 p.(Pro189Ser), as well as, previously described variants identified in genes GJA3, GJA8, CRYAA, BFSP1, PITX3, COL4A1 and HSF4. Additionally, eight variants of uncertain significance with evidence towards pathogenicity were identified in genes: GJA3, GJA8, LEMD2, PRX, CRYBB1, BFSP2, and MIP. 

Conclusion: These findings expand the genotype-phenotype correlations of both pathogenic and benign variation in cataract-associated genes. They further emphasise the need to develop additional evidence such as functional assays and variant classification criteria specific to paediatric cataract genes to improve interpretation of variants and molecular diagnosis in patients.

Original languageEnglish
Article numbere001064
Number of pages9
JournalBMJ Open Ophthalmology
Issue number1
Publication statusPublished - 26 Aug 2022


  • Child health (paediatrics)
  • Experimental & laboratory
  • Genetics
  • Lens and zonules


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