MED12 missense mutation in a three-generation family. Clinical characterization of MED12-related disorders and literature review

Eur J Med Genet. 2020 Mar;63(3):103768. doi: 10.1016/j.ejmg.2019.103768. Epub 2019 Sep 16.

Abstract

Mutations in MED12 gene have been described in association with syndromic and non-syndromic X-linked intellectual disability (XLID). Up to date at least three distinct XLID syndromes have been described: FG syndrome, Lujan-Fryns syndrome (LS) and Ohdo syndrome (OSMKB). In the last years, thanks to the massive use of next generation sequencing techniques (NGS) it has been possible to discover at least 16 others MED12 mutations and to expand the phenotype of MED12-related disorders. Here we report three subjects from a large non-consanguineous family presenting with a mild to severe ID, important speech delay, behavior problems, dysmorphic facial features and hearing loss. NGS allows us to detect the MED12 missense variant c.3883C > T (p.(Arg1295Cys)) carried by the three patients. This variant has been reported in 2016 by Hu et al. in one family from a big cohort of XLID families. This clinical report contributes to expanding the phenotype associated with MED12-mutations.

Keywords: Hearing loss; Intellectual disability; MED12; NGS; X-linked.

Publication types

  • Case Reports
  • Letter
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / physiopathology
  • Adolescent
  • Agenesis of Corpus Callosum / genetics*
  • Agenesis of Corpus Callosum / physiopathology
  • Anus, Imperforate / genetics*
  • Anus, Imperforate / physiopathology
  • Blepharophimosis / genetics*
  • Blepharophimosis / physiopathology
  • Blepharoptosis / genetics*
  • Blepharoptosis / physiopathology
  • Child
  • Constipation / genetics*
  • Constipation / physiopathology
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / physiopathology
  • Genes, X-Linked
  • Hearing Loss / genetics
  • Hearing Loss / physiopathology
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / physiopathology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Male
  • Marfan Syndrome / genetics*
  • Marfan Syndrome / physiopathology
  • Mediator Complex / genetics*
  • Mental Retardation, X-Linked / genetics*
  • Mental Retardation, X-Linked / physiopathology
  • Middle Aged
  • Muscle Hypotonia / congenital*
  • Muscle Hypotonia / genetics
  • Muscle Hypotonia / physiopathology
  • Mutation, Missense
  • Pedigree

Substances

  • MED12 protein, human
  • Mediator Complex

Supplementary concepts

  • Blepharophimosis syndrome Ohdo type
  • Lujan Fryns syndrome
  • Opitz-Kaveggia syndrome