RT Journal Article
SR Electronic
T1 Pathogenic genetic variants identified in Australian families with paediatric cataract
JF BMJ Open Ophthalmology
JO BMJ Open Ophth
FD BMJ Publishing Group Ltd
SP e001064
DO 10.1136/bmjophth-2022-001064
VO 7
IS 1
A1 Johanna L Jones
A1 Bennet J McComish
A1 Sandra E Staffieri
A1 Emmanuelle Souzeau
A1 Lisa S Kearns
A1 James E Elder
A1 Jac C Charlesworth
A1 David A Mackey
A1 Jonathan B Ruddle
A1 Deepa Taranath
A1 John Pater
A1 Theresa Casey
A1 Jamie E Craig
A1 Kathryn P Burdon
YR 2022
UL http://bmjophth.bmj.com/content/7/1/e001064.abstract
AB 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.Data are available on reasonable request. All variants reported in this study have been submitted to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/); ClinVar accession numbers SCV001573165-SCV001573189. Additional data can be made available on request if within the ethical bounds of this study.