Redefining the MED13L syndrome

被引：62

作者：

Adegbola, Abidemi ^{[1
,2
,3
]}

Musante, Luciana ^{[4
]}

Callewaert, Bert ^{[5
]}

Maciel, Patricia ^{[6
,7
]}

Hu, Hao ^{[4
]}

Isidor, Bertrand ^{[8
,9
]}

Picker-Minh, Sylvie ^{[10
,11
]}

Le Caignec, Cedric ^{[8
,9
]}

Delle Chiaie, Barbara ^{[5
]}

Vanakker, Olivier ^{[5
]}

Menten, Bjorn ^{[5
]}

Dheedene, Annelies ^{[5
]}

Bockaert, Nele ^{[12
]}

Roelens, Filip ^{[13
]}

Decaestecker, Karin ^{[14
]}

Silva, Joao ^{[15
]}

Soares, Gabriela ^{[16
]}

Lopes, Fatima ^{[6
,7
]}

Najmabadi, Hossein ^{[17
]}

Kahrizi, Kimia ^{[17
]}

Cox, Gerald F. ^{[18
]}

Angus, Steven P. ^{[19
]}

Staropoli, John F. ^{[20
]}

Fischer, Ute ^{[4
]}

Suckow, Vanessa ^{[4
]}

Bartsch, Oliver ^{[21
]}

Chess, Andrew ^{[1
,2
,3
]}

Ropers, Hans-Hilger ^{[4
]}

Wienker, Thomas F. ^{[4
]}

Hubner, Christoph ^{[10
]}

Kaindl, Angela M. ^{[10
,11
]}

Kalscheuer, Vera M. ^{[4
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Dev & Regenerat Biol, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA

[4] Max Planck Inst Mol Genet, Dept Human Mol Genet, D-14195 Berlin, Germany

[5] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium

[6] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga, Portugal

[7] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal

[8] CHU Nantes, Serv Genet Med, Inst Biol, F-44035 Nantes 01, France

[9] Univ Nantes, Equipe Ligue Canc 2012, Pathophysiol Bone Resorpt & Therapy Primary Bone, UMR 957,INSERM, Nantes, France

[10] Charite, Dept Pediat Neurol, D-13353 Berlin, Germany

[11] Charite, Inst Cell Biol & Neurobiol, D-13353 Berlin, Germany

[12] Ghent Univ Hosp, Pediat Neurol, Ghent, Belgium

[13] Heilig Hart Hosp, Dept Pediat, Roeselare, Belgium

[14] Stedelijk Ziekenhuis, Dept Pediat, Roeselare, Belgium

[15] IBMC, Oporto, Portugal

[16] Porto Hosp Ctr, Ctr Med Genet Dr Jacinto Magalhaes, Oporto, Portugal

[17] Univ Social Welf & Rehabil Sci, Genet Res Ctr, Tehran, Iran

[18] Boston Childrens Hosp, Dept Pediat, Div Genet, Boston, MA USA

[19] Univ N Carolina, Sch Med, Dept Pharmacol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[20] Biogen Idec Inc, Cambridge, MA USA

[21] Johannes Gutenberg Univ Mainz, Inst Human Genet, Univ Med Ctr, D-55122 Mainz, Germany

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2015年 / 23卷 / 10期

基金：

美国国家科学基金会;

关键词：

COMPARATIVE GENOMIC HYBRIDIZATION; MEDIATOR COMPLEX; INTELLECTUAL DISABILITY; GENE; MUTATION; TRANSPOSITION; STRATEGY; DEFECTS; FAMILY;

D O I：

10.1038/ejhg.2015.26

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits.

引用

页码：1308 / 1317

页数：10

共 33 条

[1] Of mice and men: molecular genetics of congenital heart disease [J].

Andersen, Troels Askhoj ;

Troelsen, Karin de Linde Lind ;

Larsen, Lars Allan .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2014, 71 (08) :1327-1352

[2] Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability [J].

Asadollahi, Reza ;

Oneda, Beatrice ;

Sheth, Frenny ;

Azzarello-Burri, Silvia ;

Baldinger, Rosa ;

Joset, Pascal ;

Latal, Beatrice ;

Knirsch, Walter ;

Desai, Soaham ;

Baumer, Alessandra ;

Houge, Gunnar ;

Andrieux, Joris ;

Rauch, Anita .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2013, 21 (10) :1100-1104

[3] Interactions between subunits of the Mediator complex with gene-specific transcription factors [J].

Borggrefe, Tilman ;

Yue, Xiaojing .

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2011, 22 (07) :759-768

[4] Across array comparative genomic hybridization: A strategy to reduce reference channel hybridizations [J].

Buffart, Tineke E. ;

Israeli, Danielle ;

Tijssen, Marianne ;

Vosse, Sjoerd J. ;

Mrsic, Alan ;

Meijer, Gerrit A. ;

Ylstra, Bauke .

GENES CHROMOSOMES & CANCER, 2008, 47 (11) :994-1004

[5] Challenges for CNV interpretation in clinical molecular karyotyping: Lessons learned from a 1001 sample experience [J].

Buysse, Karen ;

Delle Chiaie, Barbara ;

Van Coster, Rudy ;

Loeys, Bart ;

De Paepe, Anne ;

Mortier, Geert ;

Speleman, Frank ;

Menten, Bjoern .

EUROPEAN JOURNAL OF MEDICAL GENETICS, 2009, 52 (06) :398-403

[6] The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator [J].

Davis, Michael A. ;

Larimore, Elizabeth A. ;

Fissel, Brian M. ;

Swanger, Jherek ;

Taatjes, Dylan J. ;

Clurman, Bruce E. .

GENES & DEVELOPMENT, 2013, 27 (02) :151-156

[7] DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources [J].

Firth, Helen V. ;

Richards, Shola M. ;

Bevan, A. Paul ;

Clayton, Stephen ;

Corpas, Manuel ;

Rajan, Diana ;

Van Vooren, Steven ;

Moreau, Yves ;

Pettett, Roger M. ;

Carter, Nigel P. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 84 (04) :524-533

[8]

Gilissen C, 2014, NATURE, V511, P344, DOI [10.1038/nature13394, 10.3389/fnhum.2013.00444]

[9] De Novo Mutations in Moderate or Severe Intellectual Disability [J].

Hamdan, Fadi F. ;

Srour, Myriam ;

Capo-Chichi, Jose-Mario ;

Daoud, Hussein ;

Nassif, Christina ;

Patry, Lysanne ;

Massicotte, Christine ;

Ambalavanan, Amirthagowri ;

Spiegelman, Dan ;

Diallo, Ousmane ;

Henrion, Edouard ;

Dionne-Laporte, Alexandre ;

Fougerat, Anne ;

Pshezhetsky, Alexey V. ;

Venkateswaran, Sunita ;

Rouleau, Guy A. ;

Michaud, Jacques L. .

PLOS GENETICS, 2014, 10 (10)

[10] MED23 Mutation Links Intellectual Disability to Dysregulation of Immediate Early Gene Expression [J].

Hashimoto, Satoru ;

Boissel, Sarah ;

Zarhrate, Mohammed ;

Rio, Marlene ;

Munnich, Arnold ;

Egly, Jean-Marc ;

Colleaux, Laurence .

SCIENCE, 2011, 333 (6046) :1161-1163

← 1 2 3 4 →