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dc.contributor.authorPalmer, E.E.en
dc.contributor.authorKumar, R.en
dc.contributor.authorGordon, C.T.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.R.en
dc.contributor.authorLewis, A.M.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.identifier.citationAmerican Journal of Human Genetics, 2017; 101(6):995-1005en
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.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
pubs.library.collectionGenetics publicationsen
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

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