Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/92018
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dc.contributor.authorvan Bon, B.en
dc.contributor.authorCoe, B.en
dc.contributor.authorBernier, R.en
dc.contributor.authorGreen, C.en
dc.contributor.authorGerdts, J.en
dc.contributor.authorWitherspoon, K.en
dc.contributor.authorKleefstra, T.en
dc.contributor.authorWillemsen, M.en
dc.contributor.authorKumar, R.en
dc.contributor.authorBosco, P.en
dc.contributor.authorFichera, M.en
dc.contributor.authorLi, D.en
dc.contributor.authorAmaral, D.en
dc.contributor.authorCristofoli, F.en
dc.contributor.authorPeeters, H.en
dc.contributor.authorHaan, E.en
dc.contributor.authorRomano, C.en
dc.contributor.authorMefford, H.en
dc.contributor.authorScheffer, I.en
dc.contributor.authorGecz, J.en
dc.contributor.authoret al.en
dc.date.issued2016en
dc.identifier.citationMolecular Psychiatry, 2016; 21(1):126-132en
dc.identifier.issn1359-4184en
dc.identifier.issn1476-5578en
dc.identifier.urihttp://hdl.handle.net/2440/92018-
dc.descriptionMolecular Psychiatry advance online publication 24 February 2015en
dc.description.abstractDual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) maps to the Down syndrome critical region; copy number increase of this gene is thought to have a major role in the neurocognitive deficits associated with Trisomy 21. Truncation of DYRK1A in patients with developmental delay (DD) and autism spectrum disorder (ASD) suggests a different pathology associated with loss-of-function mutations. To understand the phenotypic spectrum associated with DYRK1A mutations, we resequenced the gene in 7162 ASD/DD patients (2446 previously reported) and 2169 unaffected siblings and performed a detailed phenotypic assessment on nine patients. Comparison of our data and published cases with 8696 controls identified a significant enrichment of DYRK1A truncating mutations (P=0.00851) and an excess of de novo mutations (P=2.53 × 10(-10)) among ASD/intellectual disability (ID) patients. Phenotypic comparison of all novel (n=5) and recontacted (n=3) cases with previous case reports, including larger CNV and translocation events (n=7), identified a syndromal disorder among the 15 patients. It was characterized by ID, ASD, microcephaly, intrauterine growth retardation, febrile seizures in infancy, impaired speech, stereotypic behavior, hypertonia and a specific facial gestalt. We conclude that mutations in DYRK1A define a syndromic form of ASD and ID with neurodevelopmental defects consistent with murine and Drosophila knockout models.en
dc.description.statementofresponsibilityB W M van Bon, B P Coe, R Bernier, C Green, J Gerdts, K Witherspoon, T Kleefstra, M H Willemsen, R Kumar, P Bosco, M Fichera, D Li, D Amaral, F Cristofoli, H Peeters, E Haan, C Romano, H C Mefford, I Scheffer, J Gecz, B B A de Vries and E E Eichleren
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rights© 2015 Macmillan Publishers Limiteden
dc.subjectHumans; Microcephaly; Seizures, Febrile; Speech Disorders; Fetal Growth Retardation; Syndrome; Protein-Serine-Threonine Kinases; Cohort Studies; Siblings; Autistic Disorder; Stereotypic Movement Disorder; Phenotype; Mutation; Adolescent; Adult; Middle Aged; Child; Child, Preschool; Female; Male; Protein-Tyrosine Kinases; Young Adult; Intellectual Disabilityen
dc.titleDisruptive de novo mutations of DYRK1A lead to a syndromic form of autism and IDen
dc.typeJournal articleen
dc.identifier.rmid0030023180en
dc.identifier.doi10.1038/mp.2015.5en
dc.identifier.pubid173883-
pubs.library.collectionPaediatrics publicationsen
pubs.library.teamDS08en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidKumar, R. [0000-0001-7976-8386]en
dc.identifier.orcidHaan, E. [0000-0002-7310-5124]en
dc.identifier.orcidGecz, J. [0000-0002-7884-6861]en
Appears in Collections:Paediatrics publications

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