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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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العنوان: A 127 kb truncating deletion of PGRMC1 is a novel cause of X-linked isolated paediatric cataract
المؤلفون: Jones, J.L., Corbett, M.A., Yeaman, E., Zhao, D., Gecz, J., Gasperini, R.J., Charlesworth, J.C., Mackey, D.A., Elder, J.E., Craig, J.E., Burdon, K.P.
المصدر: http://dx.doi.org/10.1038/s41431-021-00889-8Test.
بيانات النشر: Springer Nature
سنة النشر: 2021
المجموعة: The University of Adelaide: Digital Library
مصطلحات موضوعية: Animals, Zebrafish, Humans, Cataract, Membrane Proteins, Receptors, Progesterone, Pedigree, Gene Deletion, Protein Binding, Child, Male, Sterol 14-Demethylase
الوصف: 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. ; Johanna L. Jones, Mark A. Corbett, Elise Yeaman, Duran Zhao, Jozef Gecz, Robert J. Gasperini, Jac C. Charlesworth, David A. Mackey, James E. Elder, Jamie E. Craig, Kathryn P. Burdon
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 1018-4813
1476-5438
العلاقة: http://purl.org/au-research/grants/nhmrc/GNT1185477Test; http://purl.org/au-research/grants/nhmrc/GNT1116360Test; European Journal of Human Genetics, 2021; 29(8):1206-1215; http://hdl.handle.net/2440/130508Test; Corbett, M.A. [0000-0001-9298-3072]; Gecz, J. [0000-0002-7884-6861]
DOI: 10.1038/s41431-021-00889-8
الإتاحة: https://doi.org/10.1038/s41431-021-00889-8Test
http://hdl.handle.net/2440/130508Test
حقوق: © The Author(s) 2021. This article is published with 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://creativecommonsTest. org/licenses/by/4.0/.
رقم الانضمام: edsbas.22F92669
قاعدة البيانات: BASE
الوصف
تدمد:10184813
14765438
DOI:10.1038/s41431-021-00889-8