Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/113335
Citations
Scopus Web of Science® Altmetric
?
?
Full metadata record
DC FieldValueLanguage
dc.contributor.authorPalmer, E.en
dc.contributor.authorKumar, R.en
dc.contributor.authorGordon, C.en
dc.contributor.authorShaw, M.en
dc.contributor.authorHubert, L.en
dc.contributor.authorCarroll, R.en
dc.contributor.authorRio, M.en
dc.contributor.authorMurray, L.en
dc.contributor.authorLeffler, M.en
dc.contributor.authorDudding-Byth, T.en
dc.contributor.authorOufadem, M.en
dc.contributor.authorLalani, S.en
dc.contributor.authorLewis, A.en
dc.contributor.authorXia, F.en
dc.contributor.authorTam, A.en
dc.contributor.authorWebster, R.en
dc.contributor.authorBrammah, S.en
dc.contributor.authorFilippini, F.en
dc.contributor.authorPollard, J.en
dc.contributor.authorSpies, J.en
dc.contributor.authoret al.en
dc.date.issued2017en
dc.identifier.citationAmerican Journal of Human Genetics, 2017; 101(6):995-1005en
dc.identifier.issn0002-9297en
dc.identifier.issn1537-6605en
dc.identifier.urihttp://hdl.handle.net/2440/113335-
dc.description.abstractA recurrent de novo missense variant within the C-terminal Sin3-like domain of ZSWIM6 was previously reported to cause acromelic frontonasal dysostosis (AFND), an autosomal-dominant severe frontonasal and limb malformation syndrome, associated with neurocognitive and motor delay, via a proposed gain-of-function effect. We present detailed phenotypic information on seven unrelated individuals with a recurrent de novo nonsense variant (c.2737C>T [p.Arg913Ter]) in the penultimate exon of ZSWIM6 who have severe-profound intellectual disability and additional central and peripheral nervous system symptoms but an absence of frontonasal or limb malformations. We show that the c.2737C>T variant does not trigger nonsense-mediated decay of the ZSWIM6 mRNA in affected individual-derived cells. This finding supports the existence of a truncated ZSWIM6 protein lacking the Sin3-like domain, which could have a dominant-negative effect. This study builds support for a key role for ZSWIM6 in neuronal development and function, in addition to its putative roles in limb and craniofacial development, and provides a striking example of different variants in the same gene leading to distinct phenotypes.en
dc.description.statementofresponsibilityElizabeth E. Palmer, Raman Kumar, Christopher T. Gordon … Jozef Gecz … Raman K. Sharma … Marie A. Shaw … et al.en
dc.language.isoenen
dc.publisherCell Pressen
dc.rights© 2017 American Society of Human Genetics.en
dc.subjectMandibulofacial Dysostosisen
dc.titleA recurrent de novo nonsense variant in ZSWIM6 results in severe intellectual disability without frontonasal or limb malformationsen
dc.typeJournal articleen
dc.identifier.rmid0030078489en
dc.identifier.doi10.1016/j.ajhg.2017.10.009en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1091593en
dc.identifier.pubid389072-
pubs.library.collectionGenetics publicationsen
pubs.library.teamDS10en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidKumar, R. [0000-0001-7976-8386]en
dc.identifier.orcidShaw, M. [0000-0002-5060-190X]en
dc.identifier.orcidCarroll, R. [0000-0002-6979-3710]en
dc.identifier.orcidGecz, J. [0000-0002-7884-6861]en
Appears in Collections:Genetics publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.