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

Autor: Saskia M. Maas, Frédérique Béna, Koenraad Devriendt, Nathalie Marle, Birgitte Bang, Tjitske Kleefstra, Evan E. Eichler, Andy Willaert, Suzanne Vanhauwaert, Marjolein H. Willemsen, Eva Jacobs, Laurence Faivre, Shelagh Joss, Frank Speleman, Paul Coucke, Ernie M.H.F. Bongers, Abeltje M. Polstra, David A. Koolen, Nina De Rocker, Hilde Peeters, Konstantinos Varvagiannis, Thomy de Ravel, Francesca Novara, Julien Thevenon, Filip Roelens, Nele Bockaert, Sabrina Giglio, Alexander Hoischen, Susan Zeesman, Marjolaine Willems, Zeynep Tümer, Orsetta Zuffardi, Björn Menten, Carla Rosenberg, Sarah Vergult, Małgorzata J.M. Nowaczyk
Přispěvatelé: Teacher Education, Clinical sciences, Medical Genetics, Faculty of Medicine and Pharmacy, Human Genetics, Paediatric Genetics
Rok vydání: 2015
Předmět:
Adult
Male
Adolescent
Child
preschool
Obesity/genetics
Transcription Factors/genetics
Other Research Donders Center for Medical Neuroscience [Radboudumc 0]
Gene Expression
Nerve Tissue Proteins
Biology
Bioinformatics
Aquatic organisms
Developmental psychology
Intellectual Disability
Gene Duplication
Intellectual disability
medicine
Animals
Humans
Nerve Tissue Proteins/genetics
Point Mutation
Obesity
Child
Genetic Association Studies
Genetics (clinical)
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Chromosome Mapping
Middle Aged
zebrafish
medicine.disease
Intellectual Disability/genetics
facies
Chromosomes
Human
Pair 2
Cohort studies
young adult
Female
Chromosome Deletion
Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Transcription Factors
Zdroj: Genetics in medicine, 17(6), 460-466. Lippincott Williams and Wilkins
Genetics in Medicine, 17, 460-6
Genetics in Medicine, 17, 6, pp. 460-6
ISSN: 1098-3600
DOI: 10.1038/gim.2014.124
Popis: Item does not contain fulltext 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.
Databáze: OpenAIRE
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