Variant ATRX syndrome with dysfunction of ATRX and MAGT1 genes

Federica Wolf, Valentina Trapani, Ying Qiao, Kajari Mondal, 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'Driscoll, Michael E. Zwick, Evica Rajcan-Separovic

Risultato della ricerca: Contributo in rivistaArticolo in rivista

6 Citazioni (Scopus)

Abstract

A 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 five males demonstrating intellectual disability (ID) and unusual skin findings (e.g., generalized pruritus). MAGT1 is an Mg2+ transporter previously associated with primary immunodeficiency and ID, whereas 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 Mg2+ influx. The mutation in ATRX most likely explains the ID, whereas 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.
Lingua originaleEnglish
pagine (da-a)58-62
Numero di pagine5
RivistaHuman Mutation
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • magnesium channels
  • x-linked intellectual disability

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