title: Redefining the MED13L syndrome.
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.
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Abidemi
authors.initials: A
authors.lastname: Adegbola
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Luciana
authors.initials: L
authors.lastname: Musante
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Callewaert
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Patricia
authors.initials: P
authors.lastname: Maciel
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: CHU Nantes, Service de Genetique Medicale, Institut de Biologie, Nantes, France.|INSERM, UMR 957, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, Equipe Ligue Contre le Cancer 2012, Université de Nantes, Nantes, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.affiliation: Department of Pediatric Neurology, Charité University Medicine, Berlin, Germany.|Institute of Cell Biology and Neurobiology, Charité University Medicine, Berlin, Germany.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Picker-Minh
authors.affiliation: CHU Nantes, Service de Genetique Medicale, Institut de Biologie, Nantes, France.|INSERM, UMR 957, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, Equipe Ligue Contre le Cancer 2012, Université de Nantes, Nantes, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Le Caignec
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Delle Chiaie
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Vanakker
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Björn
authors.initials: B
authors.lastname: Menten
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Dheedene
authors.affiliation: Pediatric Neurology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Bockaert
authors.affiliation: Pediatrics Department, Heilig Hart Hospital, Roeselare, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Roelens
authors.affiliation: Pediatrics Department, Stedelijk Ziekenhuis, Roeselare, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Decaestecker
authors.affiliation: Institute for Molecular and Celular Biology (IBMC), Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Silva
authors.affiliation: Center for Medical Genetics Dr Jacinto Magalhães, Porto Hospital Centre, Porto, Portugal.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Soares
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Lopes
authors.affiliation: Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
authors.affiliation: Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
authors.affiliation: Division of Genetics, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Cox
authors.affiliation: Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Angus
authors.affiliation: Biogen Idec, 12 Cambridge Center, Building 6, Cambridge, MA, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Staropoli
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Fischer
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Suckow
authors.affiliation: Institute of Human Genetics, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bartsch
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chess
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Hans-Hilger
authors.initials: HH
authors.lastname: Ropers
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.affiliation: Department of Pediatric Neurology, Charité University Medicine, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hübner
authors.affiliation: Department of Pediatric Neurology, Charité University Medicine, Berlin, Germany.|Institute of Cell Biology and Neurobiology, Charité University Medicine, Berlin, Germany.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kaindl
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kalscheuer
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D056892:Mediator Complex / Q000235:genetics*; D009123:Muscle Hypotonia / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D013577:Syndrome; D014188:Transposition of Great Vessels / Q000235:genetics
chemical_list: C480067:MED13L protein, human; D056892:Mediator Complex