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Eur J Hum Genet. 2015 Oct;23(10):1308-17. doi: 10.1038/ejhg.2015.26. Epub 2015 Mar 11.

Redefining the MED13L syndrome.

Author information

1
Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
3
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4
Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
5
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
6
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.
7
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
8
CHU Nantes, Service de Genetique Medicale, Institut de Biologie, Nantes, France.
9
INSERM, UMR 957, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, Equipe Ligue Contre le Cancer 2012, Université de Nantes, Nantes, France.
10
Department of Pediatric Neurology, Charité University Medicine, Berlin, Germany.
11
Institute of Cell Biology and Neurobiology, Charité University Medicine, Berlin, Germany.
12
Pediatric Neurology, Ghent University Hospital, Ghent, Belgium.
13
Pediatrics Department, Heilig Hart Hospital, Roeselare, Belgium.
14
Pediatrics Department, Stedelijk Ziekenhuis, Roeselare, Belgium.
15
Institute for Molecular and Celular Biology (IBMC), Porto, Portugal.
16
Center for Medical Genetics Dr Jacinto Magalhães, Porto Hospital Centre, Porto, Portugal.
17
Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
18
Division of Genetics, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
19
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
20
Biogen Idec, 12 Cambridge Center, Building 6, Cambridge, MA, USA.
21
Institute of Human Genetics, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Abstract

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.

PMID:
25758992
PMCID:
PMC4592099
DOI:
10.1038/ejhg.2015.26
[Indexed for MEDLINE]
Free PMC Article

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