Kojima Hirofumi, Wada Takahito, Seki Hiroshi, Kubota Takeo, Wakui Keiko, Fukushima Yoshimitsu
Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
Genet Test. 2008 Dec;12(4):557-61. doi: 10.1089/gte.2008.0048.
Multiple osteochondromas (MO; also referred to as hereditary multiple exostoses [HME] in the literature) is an autosomal dominant disorder characterized by benign, cartilage-capped bone tumors that grow from the metaphyses of long bones. Two genes are associated with this disease: EXT1 on 8q24.11-q24.13 and EXT2 on 11p12-p11. Mutations in EXT1 and EXT2 are found in 54-96% of patients with MO and are generally more frequent in EXT1 than in EXT2. We previously studied 43 Japanese families with MO using single-strand conformation polymorphism analysis for EXT1 and EXT2, and reported 23 families (54%) with mutations and 20 families (46%) with no mutations in these genes. Among the families with mutations, 17 families (40%) had mutations in EXT1, and 6 families (14%) had mutations in EXT2. Here we examined the same 43 Japanese families using denaturing high-performance liquid chromatography as an alternative technique. We detected five mutations, three of which are novel, in seven families in addition to the previously described mutations. In summary, we detected mutations in EXT1 or EXT2 in 30 (70%) out of 43 families. Our result suggests the presence of other gene(s) responsible for MO, at least in Japanese patients.
多发性骨软骨瘤（MO；在文献中也称为遗传性多发性骨疣 [HME]）是一种常染色体显性疾病，其特征为从长骨干骺端长出的良性、有软骨帽的骨肿瘤。有两个基因与该疾病相关：位于8q24.11 - q24.13的EXT1和位于11p12 - p11的EXT2。在54% - 96%的MO患者中发现EXT1和EXT2的突变，且EXT1的突变通常比EXT2更常见。我们之前对43个日本MO家系进行了研究，采用单链构象多态性分析检测EXT1和EXT2，报告了23个家系（54%）这些基因有突变，20个家系（46%）无突变。在有突变的家系中，17个家系（40%）EXT1有突变，6个家系（14%）EXT2有突变。在此，我们使用变性高效液相色谱作为替代技术对相同的43个日本家系进行检测。除了先前描述的突变外，我们在7个家系中检测到5个突变，其中3个是新突变。总之，我们在43个家系中的30个（70%）检测到EXT1或EXT2的突变。我们的结果表明，至少在日本患者中，存在其他与MO相关的基因。
