Histone acetylation dependent allelic expression imbalance of BAPX1 in patients with the oculo-auriculo-vertebral spectrum

Hum Mol Genet. 2006 Feb 15;15(4):581-7. doi: 10.1093/hmg/ddi474. Epub 2006 Jan 11.


The oculo-auriculo-vertebral spectrum (OAVS) (OMIM % 164210) is a common developmental disorder characterized by hemifacial microsomia, epibulbar tumours, ear malformation and vertebral anomalies. Although rare familial cases suggest that OAVS has a genetic basis, no genetic defect has been identified so far. In a patient with OAVS and a chromosomal translocation t(4;8) we have found that the chromosome 4 breakpoint is 76.4 kb distal to the BAPX1 gene, which plays an essential role in craniofacial development. We did not detect any BAPX1 mutation in 105 patients, but observed a strong allelic expression imbalance (sAEI) in fibroblasts from five of 12 patients, but not in nine normal controls (Fisher's exact test, P=0.038). sAEI was de novo in one patient and inherited in two other patients. Prolonged cell culture or treatment with the histone deacetylase inhibitor Trichostatin A led to reactivation of the downregulated allele. We propose that epigenetic dysregulation of BAPX1 plays an important role in OAVS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allelic Imbalance / drug effects
  • Allelic Imbalance / genetics*
  • Cells, Cultured
  • Chromosomes, Human, Pair 4 / genetics
  • Chromosomes, Human, Pair 8 / genetics
  • Enzyme Inhibitors / pharmacology
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Goldenhar Syndrome / enzymology
  • Goldenhar Syndrome / genetics*
  • Histone Deacetylase Inhibitors
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Hydroxamic Acids / pharmacology
  • Male
  • Pedigree
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Translocation, Genetic / genetics


  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Homeodomain Proteins
  • Hydroxamic Acids
  • NKX3-2 protein, human
  • Transcription Factors
  • trichostatin A