title: MED23-associated intellectual disability in a non-consanguineous family.
abstract: Intellectual disability (ID) is a heterogeneous condition arising from a variety of environmental and genetic factors. Among these causes are defects in transcriptional regulators. Herein, we report on two brothers in a nonconsanguineous family with novel compound heterozygous, disease-segregating mutations (NM_015979.3: [3656A > G];[4006C > T], NP_057063.2: [H1219R];[R1336X]) in MED23. This gene encodes a subunit of the Mediator complex that modulates the expression of RNA polymerase II-dependent genes. These brothers, who had profound ID, spasticity, congenital heart disease, brain abnormalities, and atypical electroencephalography, represent the first case of MED23-associated ID in a non-consanguineous family. They also expand upon the clinical features previously reported for mutations in this gene.
authors.affiliation: Office of the Clinical Director, NHGRI/NIH, Bethesda, Maryland.|NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, Maryland.
authors.forename: Aditi
authors.initials: A
authors.lastname: Trehan
authors.affiliation: Office of the Clinical Director, NHGRI/NIH, Bethesda, Maryland.|NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, Maryland.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Brady
authors.affiliation: Office of the Clinical Director, NHGRI/NIH, Bethesda, Maryland.|NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, Maryland.
authors.forename: Valerie
authors.initials: V
authors.lastname: Maduro
authors.affiliation: Office of the Clinical Director, NHGRI/NIH, Bethesda, Maryland.|NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, Maryland.
authors.forename: William P
authors.initials: WP
authors.lastname: Bone
authors.affiliation: Office of the Clinical Director, NHGRI/NIH, Bethesda, Maryland.|NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, Maryland.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Office of the Clinical Director, NHGRI/NIH, Bethesda, Maryland.|NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, Maryland.
authors.forename: Gretchen A
authors.initials: GA
authors.lastname: Golas
authors.affiliation: NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, Maryland.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Kane
authors.affiliation: National Institute of Neurological Disorder and Stroke, NIH, Bethesda, Maryland.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Lee
authors.affiliation: Pediatrics and Developmental Neuroscience, NIMH/NIH, Bethesda, Maryland.
authors.forename: Audrey
authors.initials: A
authors.lastname: Thurm
authors.affiliation: Office of the Clinical Director, NHGRI/NIH, Bethesda, Maryland.|George Washington University School of Medicine and Health Sciences, Children's National Medical Center, Washington, District of Columbia.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Gropman
authors.affiliation: Rehabilitation Medicine Department, Clinical Center, NIH, Bethesda, Maryland.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Paul
authors.affiliation: George Washington University School of Medicine and Health Sciences, Children's National Medical Center, Washington, District of Columbia.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vezina
authors.affiliation: NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, Maryland.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Markello
authors.affiliation: Office of the Clinical Director, NHGRI/NIH, Bethesda, Maryland.|NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, Maryland.
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.affiliation: NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, Maryland.
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
authors.affiliation: Office of the Clinical Director, NHGRI/NIH, Bethesda, Maryland.|NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, Maryland.
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Tifft
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D059472:Exome; D015870:Gene Expression; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D056892:Mediator Complex / Q000235:genetics*; D020125:Mutation, Missense; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D035781:Siblings
chemical_list: C492159:MED23 protein, human; D056892:Mediator Complex; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun
keywords: MED23; intellectual disability (ID); mediator complex; whole exome sequencing (WES)
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