MED13L loss-of-function variants in two patients with syndromic Pierre Robin sequence

Am J Med Genet A. 2018 Jan;176(1):181-186. doi: 10.1002/ajmg.a.38536. Epub 2017 Nov 21.

Abstract

We report two unrelated patients with Pierre Robin sequence (PRS) and a strikingly similar combination of associated features. Whole exome sequencing was performed for both patients. No single gene containing likely pathogenic point mutations in both patients could be identified, but the finding of an essential splice site mutation in mediator complex subunit 13 like (MED13L) in one patient prompted the investigation of copy number variants in MED13L in the other, leading to the identification of an intragenic deletion. Disruption of MED13L, encoding a component of the Mediator complex, is increasingly recognized as the cause of an intellectual disability syndrome with associated facial dysmorphism. Our findings suggest that MED13L-related disorders are a possible differential diagnosis for syndromic PRS.

Keywords: MED13L; Pierre Robin sequence; exome; intellectual disability; mediator.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / abnormalities
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Genetic Association Studies
  • Humans
  • Infant
  • Loss of Function Mutation*
  • Magnetic Resonance Imaging / methods
  • Male
  • Mediator Complex / genetics*
  • Phenotype
  • Pierre Robin Syndrome / diagnosis*
  • Pierre Robin Syndrome / genetics*
  • Sequence Analysis, DNA

Substances

  • MED13L protein, human
  • Mediator Complex