De Novo 5q14.3 Translocation 121.5-kb Upstream of MEF2C in a Patient With Severe Intellectual Disability and Early-Onset Epileptic Encephalopathy

被引：26

作者：

Saitsu, Hirotomo ^{[1
]}

Igarashi, Noboru ^{[2
]}

Kato, Mitsuhiro ^{[3
]}

Okada, Ippei

Kosho, Tomoki ^{[4
]}

Shimokawa, Osamu ^{[5
]}

Sasaki, Yuki ^{[5
]}

Nishiyama, Kiyomi

Tsurusaki, Yoshinori

Doi, Hiroshi

Miyake, Noriko

Harada, Naoki ^{[5
]}

Hayasaka, Kiyoshi ^{[3
]}

Matasumoto, Naomichi

机构：

[1] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[2] Toyama Prefectural Cent Hosp, Dept Pediat, Toyama, Japan

[3] Yamagata Univ, Fac Med, Dept Pediat, Yamagata 990, Japan

[4] Shinshu Univ, Sch Med, Dept Med Genet, Matsumoto, Nagano 390, Japan

[5] Mitsubishi Chem Medience Corp, Cytogenet Testing Grp B, Adv Med Sci Res Ctr, Nagasaki, Japan

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART A | 2011年 / 155A卷 / 11期

基金：

日本学术振兴会;

关键词：

MEF2C; early-onset epileptic encephalopathy; chromosomal translocation; regulatory region; SEVERE MENTAL-RETARDATION; TRANSCRIPTION FACTOR; MYOCLONIC EPILEPSY; GENE; MUTATIONS; MICRODELETION; HAPLOINSUFFICIENCY; EXPRESSION; MATURATION; INFANCY;

D O I：

10.1002/ajmg.a.34289

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Recent studies have shown that haploinsufficiency of MEF2C causes severe intellectual disability, epilepsy, hypotonia, and cerebral malformations. We report on a female patient with severe intellectual disability, early-onset epileptic encephalopathy, and hypoplastic corpus callosum, possessing a de novo balanced translocation, t(5; 15)(q13.3;q26.1). The patient showed upward gazing and tonic seizure of lower extremities followed by generalized clonic seizures at 4 months of age. Electroencephalogram showed hypsarrhythmia when asleep. By using fluorescent in situ hybridization (FISH), southern hybridization and inverse PCR, the translocation breakpoints were determined at the nucleotide level. The 5q14.3 breakpoint was localized 121.5-kb upstream of MEF2C. The 15q26.2 breakpoint was mapped 119-kb downstream of LOC91948 non-coding RNA. We speculate that the translocation may disrupt the proper regulation of MEF2C expression in the developing brain, resulting in severe intellectual disability and early-onset epileptic encephalopathy. (C) 2011 Wiley Periodicals, Inc.

引用

页码：2879 / 2884

页数：6

共 17 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]

De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy [J].

Claes, L ;

Del-Favero, J ;

Ceulemans, B ;

Lagae, L ;

Van Broeckhoven, C ;

De Jonghe, P .

AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (06) :1327-1332

[4]

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

[5]

Two patients with balanced translocations and autistic disorder: CSMD3 as a candidate gene for autism found in their common 8q23 breakpoint area [J].

Floris, Chiara ;

Rassu, Stefania ;

Boccone, Loredana ;

Gasperini, Daniela ;

Cao, Antonio ;

Crisponi, Laura .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2008, 16 (06) :696-704

[6]

What causes epileptic encephalopathy in infancy? The answer may lie in our genes [J].

Holland, Katherine D. ;

Hallinan, Barbara E. .

NEUROLOGY, 2010, 75 (13) :1132-1133

[7]

Disruption of the Serine/Threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation [J].

Kalscheuer, VM ;

Tao, J ;

Donnelly, A ;

Hollway, G ;

Schwinger, E ;

Kübart, S ;

Menzel, C ;

Hoeltzenbein, M ;

Tommerup, N ;

Eyre, H ;

Harbord, M ;

Haan, E ;

Sutherland, GR ;

Ropers, HH ;

Gécz, J .

AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 72 (06) :1401-1411

[8]

A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome) [J].

Kato, Mitsuhiro ;

Saitoh, Shinji ;

Kamei, Atsushi ;

Shiraishi, Hideaki ;

Ueda, Yuki ;

Akasaka, Manami ;

Tohyama, Jun ;

Akasaka, Noriyuki ;

Hayasaka, Kiyoshi .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (02) :361-366

[9]

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

[10]

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

← 1 2 →