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Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts
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 variant...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307513/ https://www.ncbi.nlm.nih.gov/pubmed/34345029 http://dx.doi.org/10.1038/s41433-021-01711-x |
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author | Berry, Vanita Ionides, Alex Pontikos, Nikolas Moore, Anthony T. Quinlan, Roy A. Michaelides, Michel |
author_facet | Berry, Vanita Ionides, Alex Pontikos, Nikolas Moore, Anthony T. Quinlan, Roy A. Michaelides, Michel |
author_sort | Berry, Vanita |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9307513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93075132022-07-24 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 Eye (Lond) Article 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. Nature Publishing Group UK 2021-08-03 2022-08 /pmc/articles/PMC9307513/ /pubmed/34345029 http://dx.doi.org/10.1038/s41433-021-01711-x Text en © Crown 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article 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 |
title | Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts |
title_full | Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts |
title_fullStr | Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts |
title_full_unstemmed | Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts |
title_short | Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts |
title_sort | variants in pax6, pitx3 and hsf4 causing autosomal dominant congenital cataracts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307513/ https://www.ncbi.nlm.nih.gov/pubmed/34345029 http://dx.doi.org/10.1038/s41433-021-01711-x |
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