Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity

Nina De Rocker, Sarah Vergult, David Koolen, Eva Jacobs, Alexander Hoischen, Susan Zeesman, Birgitte Bang, Frédérique Béna, Nele Bockaert, Ernie M Bongers, Thomy de Ravel, Koenraad Devriendt, Sabrina Giglio, Laurence Faivre, Shelagh Joss, Saskia Maas, Nathalie Marle, Francesca Novara, Malgorzata J M Nowaczyk, Hilde PeetersAbeltje Polstra, Filip Roelens, Carla Rosenberg, Julien Thevenon, Zeynep Tümer, Suzanne Vanhauwaert, Konstantinos Varvagiannis, Andy Willaert, Marjolein Willemsen, Marjolaine Willems, Orsetta Zuffardi, Paul Coucke, Frank Speleman, Evan E Eichler, Tjitske Kleefstra, Björn Menten

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

PURPOSE: 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.

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)460-6
Number of pages7
JournalGenetics in Medicine : Official Journal of the American College of Medical Genetics
Volume17
Issue number6
DOIs
Publication statusPublished - Jun 2015

Keywords

  • Adolescent
  • Adult
  • Animals
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Chromosome Mapping
  • Chromosomes, Human, Pair 2
  • Cohort Studies
  • Facies
  • Female
  • Gene Duplication
  • Gene Expression
  • Genetic Association Studies
  • Humans
  • Intellectual Disability/genetics
  • Male
  • Middle Aged
  • Nerve Tissue Proteins/genetics
  • Obesity/genetics
  • Point Mutation
  • Transcription Factors/genetics
  • Young Adult
  • Zebrafish

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