Vanita Berry
Pathogenic variants in the CYP21A2 gene cause isolated autosomal dominant congenital posterior polar cataracts
Berry, Vanita; Pontikos, Nikolas; Ionides, Alex; Kalitzeos, Angelos; Quinlan, Roy A.; Michaelides, Michel
Authors
Nikolas Pontikos
Alex Ionides
Angelos Kalitzeos
Roy Quinlan r.a.quinlan@durham.ac.uk
Emeritus Professor
Michel Michaelides
Abstract
Background: Congenital cataracts are the most common cause of visual impairment worldwide. Inherited cataract is a clinically and genetically heterogeneous disease. Here we report disease-causing variants in a novel gene, CYP21A2, causing autosomal dominant posterior polar cataract. Variants in this gene are known to cause autosomal recessive congenital adrenal hyperplasia (CAH). Methods: Using whole-exome sequencing (WES), we have identified disease-causing sequence variants in two families of British and Irish origin, and in two isolated cases of Asian-Indian and British origin. Bioinformatics analysis confirmed these variants as rare with damaging pathogenicity scores. Segregation was tested within the families using direct Sanger sequencing. Results: A nonsense variant NM_000500.9 c.955 C > T; p.Q319* was identified in CYP21A2 in two families with posterior polar cataract and in an isolated case with unspecified congenital cataract phenotype. This is the same variant previously linked to CAH and identified as Q318* in the literature. We have also identified a rare missense variant NM_000500.9 c.770 T > C; p.M257T in an isolated case with unspecified congenital cataract phenotype. Conclusion: This is the first report of separate sequence variants in CYP21A2 associated with congenital cataract. Our findings extend the genetic basis for congenital cataract and add to the phenotypic spectrum of CYP21A2 variants and particularly the CAH associated Q318* variant. CYP21A2 has a significant role in mineralo- and gluco-corticoid biosynthesis. These findings suggest that CYP21A2 may be important for extra-adrenal biosynthesis of aldosterone and cortisol in the eye lens.
Citation
Berry, V., Pontikos, N., Ionides, A., Kalitzeos, A., Quinlan, R. A., & Michaelides, M. (2022). Pathogenic variants in the CYP21A2 gene cause isolated autosomal dominant congenital posterior polar cataracts. Ophthalmic Genetics, 43(2), 218-223. https://doi.org/10.1080/13816810.2021.1998556
Journal Article Type | Article |
---|---|
Acceptance Date | Oct 15, 2021 |
Online Publication Date | Nov 8, 2021 |
Publication Date | 2022 |
Deposit Date | Nov 9, 2021 |
Publicly Available Date | Aug 19, 2022 |
Journal | Ophthalmic Genetics |
Print ISSN | 1381-6810 |
Electronic ISSN | 1744-5094 |
Publisher | Taylor and Francis Group |
Peer Reviewed | Peer Reviewed |
Volume | 43 |
Issue | 2 |
Pages | 218-223 |
DOI | https://doi.org/10.1080/13816810.2021.1998556 |
Public URL | https://durham-repository.worktribe.com/output/1222725 |
Files
Published Journal Article
(2.9 Mb)
PDF
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
Copyright Statement
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
You might also like
Downloadable Citations
About Durham Research Online (DRO)
Administrator e-mail: dro.admin@durham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2025
Advanced Search