title: Variant ATRX syndrome with dysfunction of ATRX and MAGT1 genes.
abstract: A 0.8 kb 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qiao
authors.forename: Kajari
authors.initials: K
authors.lastname: Mondal
authors.forename: Valentina
authors.initials: V
authors.lastname: Trapani
authors.forename: Jiadi
authors.initials: J
authors.lastname: Wen
authors.forename: Gillian
authors.initials: G
authors.lastname: Carpenter
authors.forename: Robert
authors.initials: R
authors.lastname: Wildin
authors.forename: E Magda
authors.initials: EM
authors.lastname: Price
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gibbons
authors.forename: Jennifer
authors.initials: J
authors.lastname: Eichmeyer
authors.forename: Ruby
authors.initials: R
authors.lastname: Jiang
authors.forename: Barbara
authors.initials: B
authors.lastname: DuPont
authors.forename: Sally
authors.initials: S
authors.lastname: Martell
authors.forename: Suzanne M E
authors.initials: SM
authors.lastname: Lewis
authors.forename: Wendy P
authors.initials: WP
authors.lastname: Robinson
authors.forename: Mark
authors.initials: M
authors.lastname: O'Driscoll
authors.forename: Federica I
authors.initials: FI
authors.lastname: Wolf
authors.forename: Michael E
authors.initials: ME
authors.lastname: Zwick
authors.forename: Evica
authors.initials: E
authors.lastname: Rajcan-Separovic
mesh_terms: D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D041321:Chromosomes, Human, X; D048749:Cytokinesis; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D004275:DNA, Ribosomal / Q000378:metabolism; D059472:Exome; D005260:Female; D020131:Genes, Duplicate; D006801:Humans; D007438:Introns; D008274:Magnesium / Q000378:metabolism; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D011537:Pruritus / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA; D013577:Syndrome; D000075924:X-linked Nuclear Protein
chemical_list: D027682:Cation Transport Proteins; D004275:DNA, Ribosomal; C509698:MagT1 protein, human; D009687:Nuclear Proteins; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein; D008274:Magnesium