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De novo variants predicting haploinsufficiency for DIP2C are associated with expressive speech delay.

dc.rights.licenseopenen_US
dc.contributor.authorHA, Thoa
dc.contributor.authorMORGAN, Angela
dc.contributor.authorBARTOS, Meghan N
dc.contributor.authorBEATTY, Katelyn
dc.contributor.authorCOGNÉ, Benjamin
dc.contributor.authorBRAUN, Dominique
dc.contributor.authorGERBER, Céline B
dc.contributor.authorGASPAR, Harald
dc.contributor.authorKOPPS, Anna M
dc.contributor.authorRIEUBLAND, Claudine
dc.contributor.authorHURST, Anna C E
dc.contributor.authorAMOR, David J
dc.contributor.authorNIZON, Mathilde
dc.contributor.authorPASQUIER, Laurent
dc.contributor.authorPFUNDT, Rolph
dc.contributor.authorREIS, André
dc.contributor.authorSIU, Victoria Mok
dc.contributor.authorTESSARECH, Marine
dc.contributor.authorTHOMPSON, Michelle L
dc.contributor.authorVINCENT, Marie
dc.contributor.authorDE VRIES, Bert B A
dc.contributor.authorWALSH, Matthew B
dc.contributor.authorWECHSLER, Stephanie Burns
dc.contributor.authorZWEIER, Christiane
dc.contributor.authorSCHNUR, Rhonda E
dc.contributor.authorGUILLEN SACOTO, Maria J
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorMARGOT, Henri
dc.contributor.authorMASOTTO, Barbara
dc.contributor.authorPALAFOLL, Maria Irene Valenzuela
dc.contributor.authorNAWAZ, Urwah
dc.contributor.authorVOINEAGU, Irina
dc.contributor.authorSLAVOTINEK, Anne
dc.date.accessioned2024-12-20T16:33:26Z
dc.date.available2024-12-20T16:33:26Z
dc.date.issued2024-07-01
dc.identifier.issn1552-4833en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/204056
dc.description.abstractEnThe disconnected (disco)-interacting protein 2 (DIP2) gene was first identified in D. melanogaster and contains a DNA methyltransferase-associated protein 1 (DMAP1) binding domain, Acyl-CoA synthetase domain and AMP-binding sites. DIP2 regulates axonal bifurcation of the mushroom body neurons in D. melanogaster and is required for axonal regeneration in the neurons of C. elegans. The DIP2 homologues in vertebrates, Disco-interacting protein 2 homolog A (DIP2A), Disco-interacting protein 2 homolog B (DIP2B), and Disco-interacting protein 2 homolog C (DIP2C), are highly conserved and expressed widely in the central nervous system. Although there is evidence that DIP2C plays a role in cognition, reports of pathogenic variants in these genes are rare and their significance is uncertain. We present 23 individuals with heterozygous DIP2C variants, all manifesting developmental delays that primarily affect expressive language and speech articulation. Eight patients had de novo variants predicting loss-of-function in the DIP2C gene, two patients had de novo missense variants, three had paternally inherited loss of function variants and six had maternally inherited loss-of-function variants, while inheritance was unknown for four variants. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects, and bicuspid aortic valve). Minor facial anomalies were inconsistent but included a high anterior hairline with a long forehead, broad nasal tip, and ear anomalies. Brainspan analysis showed elevated DIP2C expression in the human neocortex at 10-24 weeks after conception. With the cases presented herein, we provide phenotypic and genotypic data supporting the association between loss-of-function variants in DIP2C with a neurocognitive phenotype.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subject.enDevelopmental delay
dc.subject.enDIP2
dc.subject.enDIP2C
dc.subject.enIntellectual disability
dc.subject.enSpeech articulation
dc.subject.enSpeech delay
dc.title.enDe novo variants predicting haploinsufficiency for DIP2C are associated with expressive speech delay.
dc.title.alternativeAm J Med Genet Aen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1002/ajmg.a.63559en_US
dc.subject.halSciences du Vivant [q-bio]/Génétiqueen_US
dc.identifier.pubmed38421105en_US
bordeaux.journalAmerican Journal of Medical Genetics Part Aen_US
bordeaux.pagee63559en_US
bordeaux.volume194en_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.issue7en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04852192
hal.version1
hal.date.transferred2024-12-20T16:33:30Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccCC BY-NC-NDen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=American%20Journal%20of%20Medical%20Genetics%20Part%20A&rft.date=2024-07-01&rft.volume=194&rft.issue=7&rft.spage=e63559&rft.epage=e63559&rft.eissn=1552-4833&rft.issn=1552-4833&rft.au=HA,%20Thoa&MORGAN,%20Angela&BARTOS,%20Meghan%20N&BEATTY,%20Katelyn&COGN%C3%89,%20Benjamin&rft.genre=article


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