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Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts

Berry, Vanita; Ionides, Alex; Pontikos, Nikolas; Moore, Anthony T.; Quinlan, Roy A.; Michaelides, Michel

Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts Thumbnail


Authors

Vanita Berry

Alex Ionides

Nikolas Pontikos

Anthony T. Moore

Michel Michaelides



Abstract

Background: Lens development is orchestrated by transcription factors. Disease-causing variants in transcription factors and their developmental target genes are associated with congenital cataracts and other eye anomalies. Methods: Using whole exome sequencing, we identified disease-causing variants in two large British families and one isolated case with autosomal dominant congenital cataract. Bioinformatics analysis confirmed these disease-causing mutations as rare or novel variants, with a moderate to damaging pathogenicity score, with testing for segregation within the families using direct Sanger sequencing. Results: Family A had a missense variant (c.184 G>A; p.V62M) in PAX6 and affected individuals presented with nuclear cataract. Family B had a frameshift variant (c.470–477dup; p.A160R*) in PITX3 that was also associated with nuclear cataract. A recurrent missense variant in HSF4 (c.341 T>C; p.L114P) was associated with congenital cataract in a single isolated case. Conclusions: We have therefore identified novel variants in PAX6 and PITX3 that cause autosomal dominant congenital cataract.

Citation

Berry, V., Ionides, A., Pontikos, N., Moore, A. T., Quinlan, R. A., & Michaelides, M. (2022). Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts. Eye, 36(8), 1694-1701. https://doi.org/10.1038/s41433-021-01711-x

Journal Article Type Article
Acceptance Date Jul 16, 2021
Online Publication Date Aug 3, 2021
Publication Date 2022-08
Deposit Date Oct 25, 2021
Publicly Available Date Oct 25, 2021
Journal Eye
Print ISSN 0950-222X
Electronic ISSN 1476-5454
Publisher Springer Nature
Peer Reviewed Peer Reviewed
Volume 36
Issue 8
Pages 1694-1701
DOI https://doi.org/10.1038/s41433-021-01711-x
Public URL https://durham-repository.worktribe.com/output/1228664

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.






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