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Pathogenic genetic variants identified in Australian families with paediatric cataract


Jones, JL and McComish, BJ and Staffieri, SE and Souzeau, E and Kearns, LS and Elder, JE and Charlesworth, JC and Mackey, DA and Ruddle, JB and Taranath, D and Pater, J and Casey, T and Craig, JE and Burdon, KP, Pathogenic genetic variants identified in Australian families with paediatric cataract, BMJ Open Ophthalmology, 7, (1) pp. 1-24. ISSN 2397-3269 (2022) [Refereed Article]

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2022 Author(s) (or their employer(s)) This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license.

DOI: doi:10.1136/bmjophth-2022-001064


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 '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.

Item Details

Item Type:Refereed Article
Keywords:child health (paediatrics), experimental & laboratory, genetics, lens and zonules
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Jones, JL (Dr Johanna Jones)
UTAS Author:McComish, BJ (Dr Bennet McComish)
UTAS Author:Charlesworth, JC (Dr Jac Charlesworth)
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
ID Code:153643
Year Published:2022
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-09-29
Last Modified:2022-11-29
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