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Variant ATRX syndrome with dysfunction of ATRX and MAGT1 genes
journal contribution
posted on 2023-06-08, 16:17 authored by Ying Qiao, Kajari Mondal, Valentina Trapani, Jiadi Wen, Gillian Carpenter, Robert Wildin, E Magda Price, Richard J Gibbons, Jennifer Eichmeyer, Ruby Jiang, Barbara Dupont, Sally Martell, Suzanne M E Lewis, Wendy P Robinson, Mark O'DriscollMark O'Driscoll, Federica I Wolf, Michael E Zwick, Evica Rajcan-SeparovicA 0.8kb intronic duplication in MAGT1 and a single base pair deletion in the last exon of ATRX were identified using a chromosome X specific microarray and exome sequencing in a family with 5 males demonstrating intellectual disability (ID) and unusual skin findings (e.g. generalized pruritus). MAGT1 is a Mg(2+) transporter previously associated with primary immunodeficiency and ID, while mutations in ATRX cause ATRX-ID syndrome. In patient cells, the function of ATRX was demonstrated to be abnormal based on altered RNA/protein expression, hypomethylation of rDNA, and abnormal cytokinesis. Dysfunction of MAGT1 was reflected in reduced RNA/protein expression and Mg(2+) influx. The mutation in ATRX most likely explains the ID, while MAGT1 disruption could be linked to abnormal skin findings, as normal magnesium homeostasis is necessary for skin health. This work supports observations that multiple mutations collectively contribute to the phenotypic variability of syndromic ID, and emphasizes the importance of correlating clinical phenotype with genomic and cell function analyses. This article is protected by copyright. All rights reserved.
History
Publication status
- Published
Journal
Human mutationISSN
1059-7794Publisher
WileyExternal DOI
Issue
1Volume
35Page range
58-62Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
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- No
Peer reviewed?
- Yes
Legacy Posted Date
2013-11-06Usage metrics
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