Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/98698
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Type: Journal article
Title: Increased STAG2 dosage defines a novel cohesinopathy with intellectual disability and behavioral problems
Author: Kumar, R.
Corbett, M.
Van Bon, B.
Gardner, A.
Woenig, J.
Jolly, L.
Douglas, E.
Friend, K.
Tan, C.
Van Esch, H.
Holvoet, M.
Raynaud, M.
Field, M.
Leffler, M.
Budny, B.
Wisniewska, M.
Badura-Stronka, M.
Latos-Bieleńska, A.
Batanian, J.
Rosenfeld, J.
et al.
Citation: Human Molecular Genetics, 2015; 24(25):7171-7181
Publisher: Oxford University Press
Issue Date: 2015
ISSN: 0964-6906
1460-2083
Statement of
Responsibility: 
Raman Kumar ... Mark A. Corbett ...Alison Gardner, Joshua A.Woenig, Lachlan A. Jolly ... Chuan Tan ... Elizabeth M. Thompson, Eric Haan... Jozef Gecz et al.
Abstract: Next generation genomic technologies have made a significant contribution to the understanding of the genetic architecture of human neurodevelopmental disorders. Copy number variants (CNVs) play an important role in the genetics of intellectual disability (ID). For many CNVs, and copy number gains in particular, the responsible dosage-sensitive gene(s) have been hard to identify. We have collected 18 different interstitial microduplications and 1 microtriplication of Xq25. There were 15 affected individuals from 6 different families and 13 singleton cases, 28 affected males in total. The critical overlapping region involved the STAG2 gene, which codes for a subunit of the cohesin complex that regulates cohesion of sister chromatids and gene transcription. We demonstrate that STAG2 is the dosage-sensitive gene within these CNVs, as gains of STAG2 mRNA and protein dysregulate disease-relevant neuronal gene networks in cells derived from affected individuals. We also show that STAG2 gains result in increased expression of OPHN1, a known X-chromosome ID gene. Overall, we define a novel cohesinopathy due to copy number gain of Xq25 and STAG2 in particular.
Keywords: Chromosomes, Human, X; Humans; Antigens, Nuclear; Reverse Transcriptase Polymerase Chain Reaction; Male; DNA Copy Number Variations; Intellectual Disability; Problem Behavior
Description: First published online: October 6, 2015
Rights: © The Author 2015. Published by Oxford University Press. All rights reserved.
RMID: 0030037109
DOI: 10.1093/hmg/ddv414
Grant ID: http://purl.org/au-research/grants/nhmrc/628952
http://purl.org/au-research/grants/nhmrc/1041920
Appears in Collections:Paediatrics publications

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