title: Histone acetylation dependent allelic expression imbalance of BAPX1 in patients with the oculo-auriculo-vertebral spectrum.
abstract: 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.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, 45122 Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Fischer
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Lüdecke
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.forename: Stefan
authors.initials: S
authors.lastname: Böhringer
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
mesh_terms: D022981:Allelic Imbalance / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006053:Goldenhar Syndrome / Q000201:enzymology / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D018398:Homeodomain Proteins; D006877:Hydroxamic Acids; C491536:NKX3-2 protein, human; D014157:Transcription Factors; C012589:trichostatin A