Pathogenic genetic variants identified in Australian families with paediatric cataract

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 Austral...

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Autores principales: Jones, Johanna L, McComish, Bennet J, Staffieri, Sandra E, Souzeau, Emmanuelle, Kearns, Lisa S, Elder, James E, Charlesworth, Jac C, Mackey, David A, Ruddle, Jonathan B, Taranath, Deepa, Pater, John, Casey, Theresa, Craig, Jamie E, Burdon, Kathryn P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9422809/
https://www.ncbi.nlm.nih.gov/pubmed/36161833
http://dx.doi.org/10.1136/bmjophth-2022-001064
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author Jones, Johanna L
McComish, Bennet J
Staffieri, Sandra E
Souzeau, Emmanuelle
Kearns, Lisa S
Elder, James E
Charlesworth, Jac C
Mackey, David A
Ruddle, Jonathan B
Taranath, Deepa
Pater, John
Casey, Theresa
Craig, Jamie E
Burdon, Kathryn P
author_facet Jones, Johanna L
McComish, Bennet J
Staffieri, Sandra E
Souzeau, Emmanuelle
Kearns, Lisa S
Elder, James E
Charlesworth, Jac C
Mackey, David A
Ruddle, Jonathan B
Taranath, Deepa
Pater, John
Casey, Theresa
Craig, Jamie E
Burdon, Kathryn P
author_sort Jones, Johanna L
collection PubMed
description 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.
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spelling pubmed-94228092022-09-12 Pathogenic genetic variants identified in Australian families with paediatric cataract Jones, Johanna L McComish, Bennet J Staffieri, Sandra E Souzeau, Emmanuelle Kearns, Lisa S Elder, James E Charlesworth, Jac C Mackey, David A Ruddle, Jonathan B Taranath, Deepa Pater, John Casey, Theresa Craig, Jamie E Burdon, Kathryn P BMJ Open Ophthalmol Genetics 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. BMJ Publishing Group 2022-08-26 /pmc/articles/PMC9422809/ /pubmed/36161833 http://dx.doi.org/10.1136/bmjophth-2022-001064 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Genetics
Jones, Johanna L
McComish, Bennet J
Staffieri, Sandra E
Souzeau, Emmanuelle
Kearns, Lisa S
Elder, James E
Charlesworth, Jac C
Mackey, David A
Ruddle, Jonathan B
Taranath, Deepa
Pater, John
Casey, Theresa
Craig, Jamie E
Burdon, Kathryn P
Pathogenic genetic variants identified in Australian families with paediatric cataract
title Pathogenic genetic variants identified in Australian families with paediatric cataract
title_full Pathogenic genetic variants identified in Australian families with paediatric cataract
title_fullStr Pathogenic genetic variants identified in Australian families with paediatric cataract
title_full_unstemmed Pathogenic genetic variants identified in Australian families with paediatric cataract
title_short Pathogenic genetic variants identified in Australian families with paediatric cataract
title_sort pathogenic genetic variants identified in australian families with paediatric cataract
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9422809/
https://www.ncbi.nlm.nih.gov/pubmed/36161833
http://dx.doi.org/10.1136/bmjophth-2022-001064
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