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dc.contributor.authorHarris, J
dc.contributor.authorMahone, E M
dc.contributor.authorBjornsson, H T
dc.date.accessioned2019-06-21T14:05:46Z
dc.date.available2019-06-21T14:05:46Z
dc.date.issued2019-06
dc.date.submitted2019-06
dc.identifier.citationMolecularly confirmed Kabuki (Niikawa-Kuroki) syndrome patients demonstrate a specific cognitive profile with extensive visuospatial abnormalities. 2019, 63(6):489-497 J Intellect Disabil Resen_US
dc.identifier.issn1365-2788
dc.identifier.pmid30767315
dc.identifier.doi10.1111/jir.12596
dc.identifier.urihttp://hdl.handle.net/2336/620951
dc.descriptionTo access publisher's full text version of this article click on the hyperlink belowen_US
dc.description.abstractBACKGROUND: Kabuki (Niikawa-Kuroki) syndrome (KS) is caused by disease-causing variants in either of two components (KMT2D and KDM6A) of the histone methylation machinery. Nearly all individuals with KS have cognitive difficulties, and most have intellectual disability. Recent studies on a mouse model of KS suggest disruption of normal adult neurogenesis in the granule cell layer of the dentate gyrus of the hippocampus. These mutant mice also demonstrate hippocampal memory defects compared with littermates, but this phenotype is rescued postnatally with agents that target the epigenetic machinery. If these findings are relevant to humans with KS, we would expect significant and disproportionate disruption of visuospatial functioning in these individuals. METHODS: To test this hypothesis, we have compiled a battery to robustly explore visuospatial function. We prospectively recruited 22 patients with molecularly confirmed KS and 22 IQ-matched patients with intellectual disability. RESULTS: We observed significant deficiencies in visual motor, visual perception and visual motor memory in the KS group compared with the IQ-matched group on several measures. In contrast, language function appeared to be marginally better in the KS group compared with the IQ-matched group in a sentence comprehension task. CONCLUSIONS: Together, our data suggest specific disruption of visuospatial function, likely linked to the dentate gyrus, in individuals with KS and provide the groundwork for a novel and specific outcome measure for a clinical trial in a KS population.en_US
dc.description.sponsorshipNational Institute of Health Intellectual and Developmental Disabilities Center at Kennedy Krieger/Johns Hopkins University Louma G. Foundationen_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.urlhttps://onlinelibrary.wiley.com/doi/full/10.1111/jir.12596en_US
dc.subjectKMT2Den_US
dc.subjectdentate gyrusen_US
dc.subjectepigeneticsen_US
dc.subjecthistone machineryen_US
dc.subjectintellectual disabilityen_US
dc.subjectneurocognitive testingen_US
dc.subjectKabuki heilkennien_US
dc.subjectSjóngallaren_US
dc.subject.meshIntellectual Disabilityen_US
dc.subject.meshVision Disordersen_US
dc.titleMolecularly confirmed Kabuki (Niikawa-Kuroki) syndrome patients demonstrate a specific cognitive profile with extensive visuospatial abnormalities.en_US
dc.typeArticleen_US
dc.contributor.department1 Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA. 2 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA. 3 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 4 Department of Neuropsychology, Kennedy Krieger Institute, Baltimore, MD, USA. 5 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 6 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 7 Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik, Iceland.en_US
dc.identifier.journalJournal of intellectual disability researchen_US
dc.rights.accessNational Consortium - Landsaðganguren_US
dc.departmentcodeMAB12
dc.source.journaltitleJournal of intellectual disability research : JIDR


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