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


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Jones, JL ORCID: 0000-0002-6475-9134, Corbett, MA, Yeaman, E, Zhao, D, Gecz, J, Gasperini, RJ ORCID: 0000-0001-6859-1247, Charlesworth, JC ORCID: 0000-0001-6201-3518, Mackey, DA, Elder, JE, Craig, JE and Burdon, KP ORCID: 0000-0001-8217-1249 2021 , 'A 127 kb truncating deletion of PGRMC1 is a novel cause of X-linked isolated paediatric cataract' , European Journal of Human Genetics , doi: 10.1038/s41431-021-00889-8.

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Inherited paediatric cataract is a rare Mendelian disease that results in visual impairment or blindness due to a clouding of theeye’s crystalline lens. Here we report an Australian family with isolated paediatric cataract, which we had previouslymapped to Xq24. Linkage at Xq24–25 (LOD = 2.53) was confirmed, and the region refined with a denser marker map. Inaddition, 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. Thisdeletion completely removed a commonly deleted long non-coding RNA gene LOC101928336 and truncated the proteincoding progesterone receptor membrane component 1 (PGRMC1) gene following exon 1. A literature search revealed areport of two unrelated males with non-syndromic intellectual disability, as well as congenital cataract, who had contiguousgene deletions that accounted for their intellectual disability but also disrupted the PGRMC1 gene. A morpholino-inducedpgrmc1 knockdown in a zebrafish model produced significant cataract formation, supporting a role for PGRMC1 in lensdevelopment 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 isthe truncating deletion of PGRMC1, which we report as a novel cataract gene.

Item Type: Article
Authors/Creators: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
Keywords: cataract, gene
Journal or Publication Title: European Journal of Human Genetics
Publisher: Nature Publishing Group
ISSN: 1018-4813
DOI / ID Number: 10.1038/s41431-021-00889-8
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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.

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