Constitutional rearrangement of the architectural factor HMGA2:: A novel human phenotype including overgrowth and lipomas
Constitutional rearrangement of the architectural factor HMGA2:: A novel human phenotype including overgrowth and lipomas
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DOI：
10.1086/427565
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发表时间：
2005-02-01
影响因子：
9.8
通讯作者：
Morton, CC
中科院分区：
文献类型：
--
作者：
Ligon, AH;Moore, SDP;Morton, CC
尽管许多基因的体细胞突变与人类肿瘤（如脂肪瘤）的发生有关，但这些基因中生殖系突变的例子相对较少。在这里，我们描述了一个8岁的男孩谁有一个从头12号染色体臂间倒位，断点在p11.22和q14.3，和表型，包括极端的躯体过度生长，先进的软骨内骨和牙齿年龄，小脑肿瘤，多发性脂肪瘤。他的染色体倒位被发现截短HMGA2，HMGA2是一种编码与许多良性间叶肿瘤的病因学有关的结构因子的基因，并映射到12q14.3断点。在转基因小鼠中，类似的鼠Hmga2截短导致体细胞过度生长，特别是脂肪和脂肪瘤丰度增加，这些特征与在儿童中观察到的特征惊人相似。这代表了影响HMGA2的宪法重排的第一份报告，并证明了该基因在人类生长和发育中的作用。对该儿童的系统遗传分析和临床研究可能会为HMGA 2在脂肪生成、骨生成和一般生长控制中的作用提供独特的见解。
Although somatic mutations in a number of genes have been associated with development of human tumors, such as lipomas, relatively few examples exist of germline mutations in these genes. Here we describe an 8-year-old boy who has a de novo pericentric inversion of chromosome 12, with breakpoints at p11.22 and q14.3, and a phenotype including extreme somatic overgrowth, advanced endochondral bone and dental ages, a cerebellar tumor, and multiple lipomas. His chromosomal inversion was found to truncate HMGA2, a gene that encodes an architectural factor involved in the etiology of many benign mesenchymal tumors and that maps to the 12q14.3 breakpoint. Similar truncations of murine Hmga2 in transgenic mice result in somatic overgrowth and, in particular, increased abundance of fat and lipomas, features strikingly similar to those observed in the child. This represents the first report of a constitutional rearrangement affecting HMGA2 and demonstrates the role of this gene in human growth and development. Systematic genetic analysis and clinical studies of this child may offer unique insights into the role of HMGA2 in adipogenesis, osteogenesis, and general growth control.