MED23-associated intellectual disability in a non-consanguineous family

• Published in: American journal of medical genetics. Part A Vol. 167A; no. 6; pp. 1374 - 1380
• Main Authors: Trehan, Aditi, Brady, Jacqueline M., Maduro, Valerie, Bone, William P., Huang, Yan, Golas, Gretchen A., Kane, Megan S., Lee, Paul R., Thurm, Audrey, Gropman, Andrea L., Paul, Scott M., Vezina, Gilbert, Markello, Thomas C., Gahl, William A., Boerkoel, Cornelius F., Tifft, Cynthia J.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.06.2015; Wiley Subscription Services, Inc
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Abnormalities, Multiple - pathology; Child; Child, Preschool; Exome; Gene Expression; Heart Defects, Congenital - diagnosis; Heart Defects, Congenital - genetics; Heart Defects, Congenital - pathology; Heterozygote; High-Throughput Nucleotide Sequencing; Humans; intellectual disability (ID); Intellectual Disability - diagnosis; Intellectual Disability - genetics; Intellectual Disability - pathology; Male; MED23; mediator complex; Mediator Complex - genetics; Mutation, Missense; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; Siblings; whole exome sequencing (WES); MED23; mediator complex; intellectual disability (ID); whole exome sequencing (WES)
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.37047

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. © 2015 Wiley Periodicals, Inc.