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


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, (, 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


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:3
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-06-08
Last Modified:2021-09-02
Downloads:19 View Download Statistics

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