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dc.contributor.authorScala, Marcello
dc.contributor.authorAnijs, Midas
dc.contributor.authorBattini, Roberta
dc.contributor.authorMadia, Francesca
dc.contributor.authorCapra, Valeria
dc.contributor.authorScudieri, Paolo
dc.contributor.authorVerrotti, Alberto
dc.contributor.authorZara, Federico
dc.contributor.authorMinetti, Carlo
dc.contributor.authorVernes, Sonja C.
dc.contributor.authorStriano, Pasquale
dc.identifier.citationScala , M , Anijs , M , Battini , R , Madia , F , Capra , V , Scudieri , P , Verrotti , A , Zara , F , Minetti , C , Vernes , S C & Striano , P 2021 , ' Hyperkinetic stereotyped movements in a boy with biallelic CNTNAP2 variants ' , Italian Journal of Pediatrics , vol. 47 , 208 .
dc.identifier.otherPURE: 276266786
dc.identifier.otherPURE UUID: 1dd7a546-f53d-4f25-ab7d-d8d9a26a8d9d
dc.identifier.otherRIS: urn:6CC1FB6911B3EA14DC03CC1A90CF1B5A
dc.identifier.otherRIS: Scala2021
dc.identifier.otherORCID: /0000-0003-0305-4584/work/101582021
dc.descriptionSCV was supported by a Max Planck Research Group awarded by the Max Planck Gesellschaft, a Human Frontiers Science Program Grant (RGP0058/2016), and a UKRI Future Leaders Fellowship (MR/T021985/1). MA was supported by an International Max Planck Research School (IMPRS) PhD Fellowship from the Max Planck Institute for Psycholinguistics.en
dc.description.abstractBackground:  Heterozygous variants in CNTNAP2 have been implicated in a wide range of neurological phenotypes, including intellectual disability (ID), epilepsy, autistic spectrum disorder (ASD), and impaired language. However, heterozygous variants can also be found in unaffected individuals. Biallelic CNTNAP2 variants are rarer and cause a well-defined genetic syndrome known as CASPR2 deficiency disorder, a condition characterised by ID, early-onset refractory epilepsy, language impairment, and autistic features. Case-report : A 7-year-old boy presented with hyperkinetic stereotyped movements that started during early infancy and persisted over childhood. Abnormal movements consisted of rhythmic and repetitive shaking of the four limbs, with evident stereotypic features. Additional clinical features included ID, attention deficit-hyperactivity disorder (ADHD), ASD, and speech impairment, consistent with CASPR2 deficiency disorder. Whole-genome array comparative genomic hybridization detected a maternally inherited 0.402 Mb duplication, which involved intron 1, exon 2, and intron 2 of CNTNAP2 (c.97 +?_209-?dup). The affected region in intron 1 contains a binding site for the transcription factor FOXP2, potentially leading to abnormal CNTNAP2 expression regulation. Sanger sequencing of the coding region of CNTNAP2 also identified a paternally-inherited missense variant c.2752C > T, p.(Leu918Phe). Conclusion : This case expands the molecular and phenotypic spectrum of CASPR2 deficiency disorder, suggesting that Hyperkinetic stereotyped movements may be a rare, yet significant, clinical feature of this complex neurological disorder. Furthermore, the identification of an in-frame, largely non-coding duplication in CNTNAP2 points to a sophisticated underlying molecular mechanism, likely involving impaired FOXP2 binding.
dc.relation.ispartofItalian Journal of Pediatricsen
dc.rightsCopyright © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en
dc.subjectIntragenic duplicationen
dc.subjectHyperkinetic movemment disorderen
dc.subjectSpeech impairmenten
dc.subjectIntellectual disabilityen
dc.subjectQH301 Biologyen
dc.subjectQH426 Geneticsen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.titleHyperkinetic stereotyped movements in a boy with biallelic CNTNAP2 variantsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.description.statusPeer revieweden

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