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.

Qiao, Y., Mondal, K., Trapani, V., Wen, J., Carpenter, G., Wildin, R., Price, E., Gibbons, R., Eichmeyer, J., Jiang, R., Dupont, B., Martell, S., Lewis, S., Robinson, W., O'Driscoll, M., Wolf, F., Zwick, M., Rajcan Separovic, E., Variant ATRX syndrome with dysfunction of ATRX and MAGT1 genes, <<HUMAN MUTATION>>, 2014; (35): 58-62. [doi:10.1002/humu.22465] [http://hdl.handle.net/10807/76573]

Variant ATRX syndrome with dysfunction of ATRX and MAGT1 genes

Trapani, Valentina;Wolf, Federica;
2014

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.
Inglese
Qiao, Y., Mondal, K., Trapani, V., Wen, J., Carpenter, G., Wildin, R., Price, E., Gibbons, R., Eichmeyer, J., Jiang, R., Dupont, B., Martell, S., Lewis, S., Robinson, W., O'Driscoll, M., Wolf, F., Zwick, M., Rajcan Separovic, E., Variant ATRX syndrome with dysfunction of ATRX and MAGT1 genes, <<HUMAN MUTATION>>, 2014; (35): 58-62. [doi:10.1002/humu.22465] [http://hdl.handle.net/10807/76573]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/76573
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