Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/100008
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dc.contributor.authorMoey, C.en
dc.contributor.authorHinze, S.en
dc.contributor.authorBrueton, L.en
dc.contributor.authorMorton, J.en
dc.contributor.authorMcMullan, D.en
dc.contributor.authorKamien, B.en
dc.contributor.authorBarnett, C.en
dc.contributor.authorBrunetti-Pierri, N.en
dc.contributor.authorNicholl, J.en
dc.contributor.authorGecz, J.en
dc.contributor.authorShoubridge, C.en
dc.date.issued2016en
dc.identifier.citationEuropean Journal of Human Genetics, 2016; 24(3):373-380en
dc.identifier.issn1018-4813en
dc.identifier.issn1476-5438en
dc.identifier.urihttp://hdl.handle.net/2440/100008-
dc.description.abstractCopy number variations are a common cause of intellectual disability (ID). Determining the contribution of copy number variants (CNVs), particularly gains, to disease remains challenging. Here, we report four males with ID with sub-microscopic duplications at Xp11.2 and review the few cases with overlapping duplications reported to date. We established the extent of the duplicated regions in each case encompassing a minimum of three known disease genes TSPYL2, KDM5C and IQSEC2 with one case also duplicating the known disease gene HUWE1. Patients with a duplication encompassing TSPYL2, KDM5C and IQSEC2 without gains of nearby SMC1A and HUWE1 genes have not been reported thus far. All cases presented with ID and significant deficits of speech development. Some patients also manifested behavioral disturbances such as hyperactivity and attention-deficit/hyperactivity disorder. Lymphoblastic cell lines from patients show markedly elevated levels of TSPYL2, KDM5C and SMC1A, transcripts consistent with the extent of their CNVs. The duplicated region in our patients contains several genes known to escape X-inactivation, including KDM5C, IQSEC2 and SMC1A. In silico analysis of expression data in selected gene expression omnibus series indicates that dosage of these genes, especially IQSEC2, is similar in males and females despite the fact they escape from X-inactivation in females. Taken together, the data suggest that gains in Xp11.22 including IQSEC2 cause ID and are associated with hyperactivity and attention-deficit/hyperactivity disorder, and are likely to be dosage-sensitive in males.en
dc.description.statementofresponsibilityChing Moey, Susan J Hinze, Louise Brueton, Jenny Morton, Dominic J McMullan, Benjamin Kamien, Christopher P Barnett, Nicola Brunetti-Pierri, Jillian Nicholl, Jozef Gecz and Cheryl Shoubridgeen
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rights© 2016 Macmillan Publishers Limited All rights reserved 1018-4813/16en
dc.subjectChromosomes, Human, X; Humans; Guanine Nucleotide Exchange Factors; Cell Cycle Proteins; Nuclear Proteins; Chromosomal Proteins, Non-Histone; RNA, Messenger; Pedigree; Behavior; Gene Expression Regulation; Adolescent; Child; Child, Preschool; Infant; Infant, Newborn; Female; Male; Young Adult; Histone Demethylases; Chromosome Duplication; Intellectual Disability; Neurodevelopmental Disordersen
dc.titleXp11.2 microduplications including IQSEC2, TSPYL2 and KDM5C genes in patients with neurodevelopmental disordersen
dc.typeJournal articleen
dc.identifier.rmid0030030637en
dc.identifier.doi10.1038/ejhg.2015.123en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1006586en
dc.relation.granthttp://purl.org/au-research/grants/arc/FT120100086en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1041920en
dc.identifier.pubid190278-
pubs.library.collectionMedicine publicationsen
pubs.library.teamDS06en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidGecz, J. [0000-0002-7884-6861]en
dc.identifier.orcidShoubridge, C. [0000-0002-0157-3084]en
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