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A 127 kb truncating deletion of PGRMC1 is a novel cause of X-linked isolated paediatric cataract

Citation

Jones, JL and Corbett, MA and Yeaman, E and Zhao, D and Gecz, J and Gasperini, RJ and Charlesworth, JC and Mackey, DA and Elder, JE and Craig, JE and Burdon, KP, A 127 kb truncating deletion of PGRMC1 is a novel cause of X-linked isolated paediatric cataract, European Journal of Human Genetics ISSN 1018-4813 (2021) [Refereed Article]


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© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License, (https://creativecommons.org/licenses/by/4.0/), 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.

DOI: doi:10.1038/s41431-021-00889-8

Abstract

Inherited paediatric cataract is a rare Mendelian disease that results in visual impairment or blindness due to a clouding of the eye’s crystalline lens. Here we report an Australian family with isolated paediatric cataract, which we had previously mapped to Xq24. Linkage at Xq24–25 (LOD = 2.53) was confirmed, and the region refined with a denser marker map. In addition, two autosomal regions with suggestive evidence of linkage were observed. A segregating 127 kb deletion (chrX: g.118373226_118500408del) in the Xq24–25 linkage region was identified from whole-genome sequencing data. This deletion completely removed a commonly deleted long non-coding RNA gene LOC101928336 and truncated the protein coding progesterone receptor membrane component 1 (PGRMC1) gene following exon 1. A literature search revealed a report of two unrelated males with non-syndromic intellectual disability, as well as congenital cataract, who had contiguous gene deletions that accounted for their intellectual disability but also disrupted the PGRMC1 gene. A morpholino-induced pgrmc1 knockdown in a zebrafish model produced significant cataract formation, supporting a role for PGRMC1 in lens development and cataract formation. We hypothesise that the loss of PGRMC1 causes cataract through disrupted PGRMC1- CYP51A1 protein–protein interactions and altered cholesterol biosynthesis. The cause of paediatric cataract in this family is the truncating deletion of PGRMC1, which we report as a novel cataract gene.

Item Details

Item Type:Refereed Article
Keywords:cataract, gene
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biomedical and clinical sciences
UTAS Author:Jones, JL (Dr Johanna Jones)
UTAS Author:Yeaman, E (Ms Elise Yeaman)
UTAS Author:Zhao, D (Ms Duran Zhao)
UTAS Author:Gasperini, RJ (Dr Rob Gasperini)
UTAS Author:Charlesworth, JC (Dr Jac Charlesworth)
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
ID Code:144750
Year Published:2021
Funding Support:National Health and Medical Research Council (1185477)
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-06-08
Last Modified:2021-09-02
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