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dc.contributor.authorKumar, R.en
dc.contributor.authorHa, T.en
dc.contributor.authorPham, D.en
dc.contributor.authorShaw, M.en
dc.contributor.authorMangelsdorf, M.en
dc.contributor.authorFriend, K.en
dc.contributor.authorHobson, L.en
dc.contributor.authorTurner, G.en
dc.contributor.authorBoyle, J.en
dc.contributor.authorField, M.en
dc.contributor.authorHackett, A.en
dc.contributor.authorCorbett, M.en
dc.contributor.authorGecz, J.en
dc.identifier.citationEuropean Journal of Human Genetics, 2016; 24(11):1612-1616en
dc.description.abstractIntellectual disability (ID) is a clinically complex and heterogeneous disorder, which has variable severity and may be associated with additional dysmorphic, metabolic, neuromuscular or psychiatric features. Although many coding variants have been implicated in ID, identification of pathogenic non-coding regulatory variants has only been achieved in a few cases to date. We identified a duplication of a guanine on chromosome X, NC_000023.10:g.69665044dupG 7 nucleotides upstream of the translational start site in the 5' untranslated region (UTR) of the known ID gene DLG3 that encodes synapse-associated protein 102 (SAP102). The dupG variant segregated with affected status in a large multigenerational family with non-syndromic X-linked ID and was predicted to disrupt folding of the mRNA. When tested on blood cells from the affected individuals, DLG3 mRNA levels were not altered, however, DLG3/SAP102 protein levels were. We also showed by dual luciferase reporter assay that the dupG variant interfered with translation. All currently known pathogenic DLG3 variants are predicted to be null, however the dupG variant likely leads to only a modest reduction of SAP102 levels accounting for the milder phenotype seen in this family.en
dc.description.statementofresponsibilityRaman Kumar, Thuong Ha, Duyen Pham, Marie Shaw, Marie Mangelsdorf, Kathryn L Friend, Lynne Hobson, Gillian Turner, Jackie Boyle, Michael Field, Anna Hackett, Mark Corbett, and Jozef Geczen
dc.publisherNature Publishing Groupen
dc.rights© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserveden
dc.subjectCell Line, Tumor; Chromosomes, Human, X; Humans; Mental Retardation, X-Linked; Nuclear Proteins; Transcription Factors; RNA, Messenger; 5' Untranslated Regions; Mutagenesis, Insertional; Pedigree; Adult; Aged; Aged, 80 and over; Middle Aged; Female; Male; HEK293 Cells; RNA Foldingen
dc.titleA non-coding variant in the 5' UTR of DLG3 attenuates protein translation to cause non-syndromic intellectual disabilityen
dc.typeJournal articleen
pubs.library.collectionMedicine publicationsen
dc.identifier.orcidKumar, R. [0000-0001-7976-8386]en
dc.identifier.orcidPham, D. [0000-0003-0664-4133]en
dc.identifier.orcidShaw, M. [0000-0002-5060-190X]en
dc.identifier.orcidCorbett, M. [0000-0001-9298-3072]en
dc.identifier.orcidGecz, J. [0000-0002-7884-6861]en
Appears in Collections:Medicine publications

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