Refining the phenotype associated with MEF2C haploinsufficiency

被引：78

作者：

Novara, F. ^{[2
]}

Beri, S. ^{[3
]}

Giorda, R. ^{[3
]}

Ortibus, E. ^{[4
]}

Nageshappa, S. ^{[1
]}

Darra, F. ^{[5
]}

dalla Bernardina, B. ^{[5
]}

Zuffardi, O. ^{[2
,6
]}

Van Esch, H. ^{[1
]}

机构：

[1] Univ Hosp Leuven, Ctr Human Genet, B-3000 Louvain, Belgium

[2] Univ Pavia, I-27100 Pavia, PV, Italy

[3] IRCCS E Medea, Bosisio Parini, Lecco, Italy

[4] Univ Hosp Leuven, Dept Pediat, B-3000 Louvain, Belgium

[5] Policlin GB Rossi, Verona, Italy

[6] IRCCS Fdn C Mondino, Pavia, Italy

来源：

CLINICAL GENETICS | 2010年 / 78卷 / 05期

关键词：

aCGH; chromosome; 5q14; 3; epilepsy; haploinsufficiency; MEF2C; microdeletion; severe mental retardation; TRANSCRIPTION FACTOR;

D O I：

10.1111/j.1399-0004.2010.01413.x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Recently, submicroscopic deletions of the 5q14.3 region have been described in patients with severe mental retardation (MR), stereotypic movements, epilepsy and cerebral malformations. Further delineation of a critical region of overlap in these patients pointed to MEF2C as the responsible gene. This finding was further reinforced by the identification of a nonsense mutation in a patient with a similar phenotype. In brain, MEF2C is essential for early neurogenesis, neuronal migration and differentiation. Here we present two additional patients with severe MR, autism spectrum disorder and epilepsy, carrying a very small deletion encompassing the MEF2C gene. This finding strengthens the role of this gene in severe MR, and enables further delineation of the clinical phenotype.

引用

页码：471 / 477

页数：7

共 9 条

[1]

MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function [J].

Barbosa, Ana C. ;

Kim, Mi-Sung ;

Ertunc, Mert ;

Adachi, Megumi ;

Nelson, Erika D. ;

McAnally, John ;

Richardson, James A. ;

Kavalali, Ege T. ;

Monteggia, Lisa M. ;

Bassel-Duby, Rhonda ;

Olson, Eric N. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (27) :9391-9396

[2]

Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion [J].

Cardoso, C. ;

Boys, A. ;

Parrini, E. ;

Mignon-Ravix, C. ;

McMahon, J. M. ;

Khantane, S. ;

Bertini, E. ;

Pallesi, E. ;

Missirian, C. ;

Zuffardi, O. ;

Novara, F. ;

Villard, L. ;

Giglio, S. ;

Chabrol, B. ;

Slater, H. R. ;

Moncla, A. ;

Scheffer, I. E. ;

Guerrini, R. .

NEUROLOGY, 2009, 72 (09) :784-792

[3]

A novel microdeletion syndrome involving 5q14.3-q15: clinical and molecular cytogenetic characterization of three patients [J].

Engels, Hartmut ;

Wohlleber, Eva ;

Zink, Alexander ;

Hoyer, Juliane ;

Ludwig, Kerstin U. ;

Brockschmidt, Felix F. ;

Wieczorek, Dagmar ;

Moog, Ute ;

Hellmann-Mersch, Birgit ;

Weber, Ruthild G. ;

Willatt, Lionel ;

Kreiss-Nachtsheim, Martina ;

Firth, Helen V. ;

Rauch, Anita .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2009, 17 (12) :1592-1599

[4]

Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number [J].

Flavell, SW ;

Cowan, CW ;

Kim, TK ;

Greer, PL ;

Lin, YX ;

Paradis, S ;

Griffith, EC ;

Hu, LS ;

Chen, CF ;

Greenberg, ME .

SCIENCE, 2006, 311 (5763) :1008-1012

[5]

MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations [J].

Le Meur, N. ;

Holder-Espinasse, M. ;

Jaillard, S. ;

Goldenberg, A. ;

Joriot, S. ;

Amati-Bonneau, P. ;

Guichet, A. ;

Barth, M. ;

Charollais, A. ;

Journel, H. ;

Auvin, S. ;

Boucher, C. ;

Kerckaert, J-P ;

David, V. ;

Manouvrier-Hanu, S. ;

Saugier-Veber, P. ;

Frebourg, T. ;

Dubourg, C. ;

Andrieux, J. ;

Bonneau, D. .

JOURNAL OF MEDICAL GENETICS, 2010, 47 (01) :22-29

[6]

Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo [J].

Li, Hao ;

Radford, Jonathan C. ;

Ragusa, Michael J. ;

Shea, Katherine L. ;

McKercher, Scott R. ;

Zaremba, Jeffrey D. ;

Soussou, Walid ;

Nie, Zhiguo ;

Kang, Yeon-Joo ;

Nakanishi, Nobuki ;

Okamoto, Shu-ichi ;

Roberts, Amanda J. ;

Schwarz, John J. ;

Lipton, Stuart A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (27) :9397-9402

[7]

Lipton SA, 2009, SCIENCE, V323, P208, DOI 10.1126/science.323.5911.208b

[8]

Identifying autism loci and genes by tracing recent shared ancestry [J].

Morrow, Eric M. ;

Yoo, Seung-Yun ;

Flavell, Steven W. ;

Kim, Tae-Kyung ;

Lin, Yingxi ;

Hill, Robert Sean ;

Mukaddes, Nahit M. ;

Balkhy, Soher ;

Gascon, Generoso ;

Hashmi, Asif ;

Al-Saad, Samira ;

Ware, Janice ;

Joseph, Robert M. ;

Greenblatt, Rachel ;

Gleason, Danielle ;

Ertelt, Julia A. ;

Apse, Kira A. ;

Bodell, Adria ;

Partlow, Jennifer N. ;

Barry, Brenda ;

Yao, Hui ;

Markianos, Kyriacos ;

Ferland, Russell J. ;

Greenberg, Michael E. ;

Walsh, Christopher A. .

SCIENCE, 2008, 321 (5886) :218-223

[9]

A calcium-regulated MEF2 surnoylation switch controls postsynaptic differentiation [J].

Shalizi, A ;

Gaudillière, B ;

Yuan, ZQ ;

Stegmüller, J ;

Shirogane, T ;

Ge, QY ;

Tan, Y ;

Schulman, B ;

Harper, JW ;

Bonni, A .

SCIENCE, 2006, 311 (5763) :1012-1017

← 1 →