title: Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity.
abstract: OBJECTIVE
  Submicroscopic deletions of chromosome band 2p25.3 are associated with intellectual disability and/or central obesity. Although MYT1L is believed to be a critical gene responsible for intellectual disability, so far no unequivocal data have confirmed this hypothesis.
  
  
  METHODS
  In this study we evaluated a cohort of 22 patients (15 sporadic patients and two families) with a 2p25.3 aberration to further refine the clinical phenotype and to delineate the role of MYT1L in intellectual disability and obesity. In addition, myt1l spatiotemporal expression in zebrafish embryos was analyzed by quantitative polymerase chain reaction and whole-mount in situ hybridization.
  
  
  RESULTS
  Complete MYT1L deletion, intragenic deletion, or duplication was observed in all sporadic patients, in addition to two patients with a de novo point mutation in MYT1L. The familial cases comprise a 6-Mb deletion in a father and his three children and a 5' MYT1L overlapping duplication in a father and his two children. Expression analysis in zebrafish embryos shows specific myt1l expression in the developing brain.
  
  
  CONCLUSIONS
  Our data strongly strengthen the hypothesis that MYT1L is the causal gene for the observed syndromal intellectual disability. Moreover, because 17 patients present with obesity/overweight, haploinsufficiency of MYT1L might predispose to weight problems with childhood onset.Genet Med 17 6, 460-466.
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Nina
authors.initials: N
authors.lastname: De Rocker
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Vergult
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Koolen
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Jacobs
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoischen
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Zeesman
authors.affiliation: Paediatric Department, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Bang
authors.affiliation: Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Béna
authors.affiliation: Center for Developmental Disorders, Ghent University Hospital, Ghent, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Bockaert
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Ernie M
authors.initials: EM
authors.lastname: Bongers
authors.affiliation: Center for Human Genetics, Leuven University Hospitals, KU Leuven, Leuven, Belgium.
authors.forename: Thomy
authors.initials: T
authors.lastname: de Ravel
authors.affiliation: Center for Human Genetics, Leuven University Hospitals, KU Leuven, Leuven, Belgium.
authors.forename: Koenraad
authors.initials: K
authors.lastname: Devriendt
authors.affiliation: Medical Genetics Unit, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Giglio
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Hôpital d'Enfants, CHU de Dijon, Dijon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.affiliation: West of Scotland Regional Genetics Service, NHS Greater Glasgow and Clyde, Southern General Hospital, Glasgow, UK.
authors.forename: Shelagh
authors.initials: S
authors.lastname: Joss
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, UVA, Amsterdam, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Maas
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Hôpital d'Enfants, CHU de Dijon, Dijon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Marle
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Novara
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Malgorzata J M
authors.initials: MJ
authors.lastname: Nowaczyk
authors.affiliation: Center for Human Genetics, Leuven University Hospitals, KU Leuven, Leuven, Belgium.
authors.forename: Hilde
authors.initials: H
authors.lastname: Peeters
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, UVA, Amsterdam, The Netherlands.
authors.forename: Abeltje
authors.initials: A
authors.lastname: Polstra
authors.affiliation: Heilig Hart Ziekenhuis Roeselare-Menen, Roeselare, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Roelens
authors.affiliation: Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Carla
authors.identifier: 0000000248879726
authors.initials: C
authors.lastname: Rosenberg
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Hôpital d'Enfants, CHU de Dijon, Dijon, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Thevenon
authors.affiliation: Center for Applied Human Molecular Genetics, Kennedy Center, University of Copenhagen, Glostrup, Denmark.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Tümer
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Vanhauwaert
authors.affiliation: Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Varvagiannis
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Andy
authors.initials: A
authors.lastname: Willaert
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Willemsen
authors.affiliation: Département de Génétique Clinique, CHRU de Montpellier, Hôpital Arnaud de Villeneuve, Montpellier, France.
authors.forename: Marjolaine
authors.initials: M
authors.lastname: Willems
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Coucke
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.affiliation: Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Tjitske
authors.initials: T
authors.lastname: Kleefstra
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Björn
authors.initials: B
authors.lastname: Menten
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D015331:Cohort Studies; D019066:Facies; D005260:Female; D020440:Gene Duplication; D015870:Gene Expression; D056726:Genetic Association Studies; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D017354:Point Mutation; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult; D015027:Zebrafish
chemical_list: C561020:MYT1L protein, human; D009419:Nerve Tissue Proteins; D014157:Transcription Factors