R368X mutation in MID1 among recurrent mutations in patients with X-linked Opitz G/BBB syndrome

Clin Dysmorphol. 2015 Jan;24(1):7-12. doi: 10.1097/MCD.0000000000000059.

Abstract

Opitz G/BBB syndrome is a genetically heterogeneous condition, with both autosomal dominant and X-linked forms. The MID1 gene is associated with X-linked Opitz G/BBB syndrome. Most mutations identified are unique, which makes it difficult to assess possible genotype/phenotype correlations. We report on a familial c.1102C>T (p.R368X) mutation in the MID1 gene, previously reported by Cox et al. (Hum Mol Genet 9:2553-2562, 2000), and document it as a recurrent mutation causing Opitz G/BBB syndrome. This mutation may result in various midline defects, including cleft lip/palate, laryngeal cleft, hypertelorism, Dandy-Walker malformation, ventricular septal defect and hypospadias in male patients, with intrafamilial variability. Seven other mutations (c.712G>T, c.829C>T, c.1108A>G, c.1444_1447dupAACA, c.1483C>T, c.1798dupC and entire gene deletions) have been previously reported as recurrent mutations. The presented family with the c.1102C>T mutation provides additional information about the clinical consequences of the nonsense mutation causing premature truncation of the protein at the level of the COS domain.

Publication types

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

MeSH terms

  • Adult
  • Amino Acid Substitution*
  • Child
  • Esophagus / abnormalities*
  • Female
  • Genetic Diseases, X-Linked / genetics
  • Humans
  • Hypertelorism / genetics*
  • Hypospadias / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Microtubule Proteins / genetics*
  • Mutation / genetics*
  • Nuclear Proteins / genetics*
  • Pedigree
  • Transcription Factors / genetics*
  • Ubiquitin-Protein Ligases

Substances

  • Microtubule Proteins
  • Nuclear Proteins
  • Transcription Factors
  • MID1 protein, human
  • Ubiquitin-Protein Ligases

Supplementary concepts

  • Hypertelorism with esophageal abnormality and hypospadias