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ZIRC
ZFIN ID: ZDB-PUB-140919-3
Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity
De Rocker, N., Vergult, S., Koolen, D., Jacobs, E., Hoischen, A., Zeesman, S., Bang, B., Béna, F., Bockaert, N., Bongers, E.M., de Ravel, T., Devriendt, K., Giglio, S., Faivre, L., Joss, S., Maas, S., Marle, N., Novara, F., Nowaczyk, M.J., Peeters, H., Polstra, A., Roelens, F., Rosenberg, C., Thevenon, J., Tümer, Z., Vanhauwaert, S., Varvagiannis, K., Willaert, A., Willemsen, M., Willems, M., Zuffardi, O., Coucke, P., Speleman, F., Eichler, E.E., Kleefstra, T., Menten, B.
Date: 2015
Source: Genetics in medicine : official journal of the American College of Medical Genetics 17(6): 460-6 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • 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
PubMed: 25232846 Full text @ Genet. Med.
FIGURES
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 advance online publication 18 September 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.124.
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