Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Refinement of the critical 2p25.3 deletion region : the role of MYT1L in intellectual disability and obesity. / De Rocker, Nina; Vergult, Sarah; Koolen, David; Jacobs, Eva; Hoischen, Alexander; Zeesman, Susan; Bang, Birgitte; Béna, Frédérique; Bockaert, Nele; Bongers, Ernie M; de Ravel, Thomy; Devriendt, Koenraad; Giglio, Sabrina; Faivre, Laurence; Joss, Shelagh; Maas, Saskia; Marle, Nathalie; Novara, Francesca; Nowaczyk, Malgorzata J M; Peeters, Hilde; Polstra, Abeltje; Roelens, Filip; Rosenberg, Carla; Thevenon, Julien; Tümer, Zeynep; Vanhauwaert, Suzanne; Varvagiannis, Konstantinos; Willaert, Andy; Willemsen, Marjolein; Willems, Marjolaine; Zuffardi, Orsetta; Coucke, Paul; Speleman, Frank; Eichler, Evan E; Kleefstra, Tjitske; Menten, Björn.
I: Genetics In Medicine, Bind 17, Nr. 6, 06.2015, s. 460-6.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Refinement of the critical 2p25.3 deletion region
T2 - the role of MYT1L in intellectual disability and obesity
AU - De Rocker, Nina
AU - Vergult, Sarah
AU - Koolen, David
AU - Jacobs, Eva
AU - Hoischen, Alexander
AU - Zeesman, Susan
AU - Bang, Birgitte
AU - Béna, Frédérique
AU - Bockaert, Nele
AU - Bongers, Ernie M
AU - de Ravel, Thomy
AU - Devriendt, Koenraad
AU - Giglio, Sabrina
AU - Faivre, Laurence
AU - Joss, Shelagh
AU - Maas, Saskia
AU - Marle, Nathalie
AU - Novara, Francesca
AU - Nowaczyk, Malgorzata J M
AU - Peeters, Hilde
AU - Polstra, Abeltje
AU - Roelens, Filip
AU - Rosenberg, Carla
AU - Thevenon, Julien
AU - Tümer, Zeynep
AU - Vanhauwaert, Suzanne
AU - Varvagiannis, Konstantinos
AU - Willaert, Andy
AU - Willemsen, Marjolein
AU - Willems, Marjolaine
AU - Zuffardi, Orsetta
AU - Coucke, Paul
AU - Speleman, Frank
AU - Eichler, Evan E
AU - Kleefstra, Tjitske
AU - Menten, Björn
PY - 2015/6
Y1 - 2015/6
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Animals
KW - Child
KW - Child, Preschool
KW - Chromosome Deletion
KW - Chromosome Mapping
KW - Chromosomes, Human, Pair 2
KW - Cohort Studies
KW - Facies
KW - Female
KW - Gene Duplication
KW - Gene Expression
KW - Genetic Association Studies
KW - Humans
KW - Intellectual Disability
KW - Male
KW - Middle Aged
KW - Nerve Tissue Proteins
KW - Obesity
KW - Point Mutation
KW - Transcription Factors
KW - Young Adult
KW - Zebrafish
U2 - 10.1038/gim.2014.124
DO - 10.1038/gim.2014.124
M3 - Journal article
C2 - 25232846
VL - 17
SP - 460
EP - 466
JO - Genetics in Medicine
JF - Genetics in Medicine
SN - 1098-3600
IS - 6
ER -
ID: 162339055