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 Peeters; Abeltje 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

doi:10.1038/gim.2014.124

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

Medical Genetics Program

27 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Genetics In Medicine
Vol/bind	17
Udgave nummer	6
Sider (fra-til)	460-6
Antal sider	7
ISSN	1098-3600
DOI	https://doi.org/10.1038/gim.2014.124
Status	Udgivet - 4 jun. 2015

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.1038/gim.2014.124

gim2014124.pdfForlagets udgivne version, 1,21 MB

Citationsformater

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. M., ... Menten, B. (2015). Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity. Genetics In Medicine, 17(6), 460-6. https://doi.org/10.1038/gim.2014.124

De Rocker, N, Vergult, S, Koolen, D, Jacobs, E, Hoischen, A, Zeesman, S, Bang, B, Béna, F, Bockaert, N, Bongers, EM, de Ravel, T, Devriendt, K, Giglio, S, Faivre, L, Joss, S, Maas, S, Marle, N, Novara, F, Nowaczyk, MJM, 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, EE, Kleefstra, T & Menten, B 2015, 'Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity', Genetics In Medicine, bind 17, nr. 6, s. 460-6. https://doi.org/10.1038/gim.2014.124

@article{d0d647c45b1c4a9b95080293ee471a09,

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

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.",

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, Male, Middle Aged, Nerve Tissue Proteins, Obesity, Point Mutation, Transcription Factors, Young Adult, Zebrafish",

author = "{De Rocker}, Nina and Sarah Vergult and David Koolen and Eva Jacobs and Alexander Hoischen and Susan Zeesman and Birgitte Bang and Fr{\'e}d{\'e}rique B{\'e}na and Nele Bockaert and Bongers, {Ernie M} and {de Ravel}, Thomy and Koenraad Devriendt and Sabrina Giglio and Laurence Faivre and Shelagh Joss and Saskia Maas and Nathalie Marle and Francesca Novara and Nowaczyk, {Malgorzata J M} and Hilde Peeters and Abeltje Polstra and Filip Roelens and Carla Rosenberg and Julien Thevenon and Zeynep T{\"u}mer and Suzanne Vanhauwaert and Konstantinos Varvagiannis and Andy Willaert and Marjolein Willemsen and Marjolaine Willems and Orsetta Zuffardi and Paul Coucke and Frank Speleman and Eichler, {Evan E} and Tjitske Kleefstra and Bj{\"o}rn Menten",

year = "2015",

month = jun,

day = "4",

doi = "10.1038/gim.2014.124",

language = "English",

volume = "17",

pages = "460--6",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "nature publishing group",

number = "6",

}

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 - 2015/6/4

Y1 - 2015/6/4

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.

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.

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

SN - 1098-3600

VL - 17

SP - 460

EP - 466

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 6

ER -

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

Abstract

FN’s Verdensmål

Adgang til dokumentet

Fingeraftryk

Citationsformater