Fischer Sven, Lüdecke Hermann-Josef, Wieczorek Dagmar, Böhringer Stefan, Gillessen-Kaesbach Gabriele, Horsthemke Bernhard
Institut für Humangenetik, Universitätsklinikum Essen, 45122 Essen, Germany.
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.
眼-耳-脊椎综合征（OAVS）（OMIM编号：164210）是一种常见的发育障碍，其特征为半侧颜面短小、眼球表面肿物、耳部畸形和椎体异常。尽管罕见的家族病例提示OAVS有遗传基础，但迄今为止尚未鉴定出遗传缺陷。在一名患有OAVS且有染色体易位t(4;8)的患者中，我们发现4号染色体断点位于BAPX1基因远端76.4 kb处，该基因在颅面发育中起关键作用。我们在105例患者中未检测到任何BAPX1突变，但在12例患者中的5例成纤维细胞中观察到强烈的等位基因表达失衡（sAEI），而在9名正常对照中未观察到（Fisher精确检验，P = 0.038）。sAEI在1例患者中为新发，在另外2例患者中为遗传。延长细胞培养时间或用组蛋白去乙酰化酶抑制剂曲古抑菌素A处理导致下调的等位基因重新激活。我们提出BAPX1的表观遗传失调在OAVS中起重要作用。
