Original research: Pathogenic genetic variants identified in Australian families with paediatric cataract

BMJ Open Ophthalmology

article

Johanna L Jones¹  Bennet J McComish¹  Sandra E Staffieri²  Emmanuelle Souzeau⁴  Lisa S Kearns²  James E Elder³  Jac C Charlesworth¹  David A Mackey⁶  Jonathan B Ruddle²  Deepa Taranath⁴  John Pater⁷  Theresa Casey⁷  Jamie E Craig⁴  Kathryn P Burdon¹ 

[1] Menzies Institute for Medical Research , University of Tasmania;Centre for Eye Research Australia , Royal Victorian Eye and Ear Hospital;Department of Ophthalmology , Royal Children's Hospital;Department of Ophthalmology , Flinders University, Flinders Medical Centre;Department of Paediatrics , University of Melbourne;Centre for Ophthalmology and Visual Science , University of Western Australia, Lions Eye Institute;Ophthalmology Department , Women’s and Children’s Hospital

关键词: Genetics;    Child health (paediatrics);    Lens and zonules;    Experimental & laboratory;   

DOI  :  10.1136/bmjophth-2022-001064

学科分类：工业工程学

来源: BMJ Publishing Group

【 摘 要 】

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.

【 授权许可】

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