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Abstract

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
Copyright Information:	© 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.
Related URLs:	UTAS Profile: Gasperini, RJ Google Scholar: Charlesworth, JC UTAS Profile: Charlesworth, JC Google Scholar: Burdon, KP UTAS Profile: Burdon, KP
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