Premium
Variant ATRX Syndrome with Dysfunction of ATRX and MAGT 1 Genes
Author(s) -
Qiao Ying,
Mondal Kajari,
Trapani Valentina,
Wen Jiadi,
Carpenter Gillian,
Wildin Robert,
Price E. Magda,
Gibbons Richard J.,
Eichmeyer Jennifer,
Jiang Ruby,
DuPont Barbara,
Martell Sally,
Lewis Suzanne M. E.,
Robinson Wendy P.,
O'Driscoll Mark,
Wolf Federica I.,
Zwick Michael E.,
RajcanSeparovic Evica
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22465
Subject(s) - atrx , biology , genetics , exon , phenotype , mutation , gene , exome sequencing
A 0.8kb intronic duplication in MAGT 1 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). MAGT 1 is an Mg 2+ 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 MAGT 1 was reflected in reduced RNA /protein expression and Mg 2+ influx. The mutation in ATRX most likely explains the ID , whereas MAGT 1 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.