MOLECULAR ANALYSIS OF LANGER-GIEDION SYNDROME

描述(改编自《调查者摘要》)：兰格-吉迪翁 综合征的特点是手部有锥形骨痂，多发 软骨性外骨瘤，身材矮小，特征 头面部畸形和智力低下。临床特点分析 Langer-Giedion综合征与Langer-Giedion综合征基本相同 毛鼻趾综合征I型，但后者不是 包括多发性骨软骨瘤，很少包括精神发育迟缓。这个 在LGS中发现的外来骨软骨病与遗传性骨软骨病基本上是相同的 多发性骨软骨病，一种常染色体显性遗传病，其特征是 骨骺旁的多发性软骨帽状外骨瘤(良性肿瘤) 附着骨的区域。这项研究项目的长期目标是 在分子水平上的基因的完整特征是 与Langer-Giedion综合征相关的表型 及相关证候遗传性多发性骨质疏松症和 毛鼻趾综合征1型。此应用程序包括 遵循三个具体目标，这三个目标是针对我们的长期目标。 首先是分离和鉴定位于LGS区域的基因 包括TRPSI和任何可能与正常心理有关的基因 功能。第二，分离和鉴定目前存在的ext2基因 11号染色体，寻找其功能如何与EXT1相关的线索。 第三，以小鼠为模型系统，分析EXT1在骨骼中的作用 发展和肿瘤发生。描述时间和空间的特征 用RNA印迹和原位杂交检测EXT1在小鼠体内的表达 杂交技术通过以下方式确定该基因在体内发挥的作用 分析EXT1基因零突变的小鼠。涉及到的基因 Langer-Giedion综合征的病理可能参与了 骨骼和结缔组织的正常发育以及正常的心理 能力。了解这些基因的功能可能会给我们 对这些重要发育过程和肿瘤的洞察 压制。Langer-Giedion基因的分子分析将是一个 这是向详细了解其职能迈出的重要一步。

DESCRIPTION (Adapted from the Investigator's Abstract): Langer-Giedion syndrome is characterized by cone-shaped epiphyses in the hand, multiple cartilaginous exostoses, shortness of stature, and characteristic craniofacial abnormalities, and mental retardation. The clinical features of Langer-Giedion syndrome are essentially identical to those of trichorhinophalangeal syndrome type I except that the latter does not include multiple exostoses and rarely includes mental retardation. The exostoses found in LGS are essentially identical to those seen in hereditary multiple exostoses, an autosomal dominant disorder characterized by multiple, cartilage-capped exostoses (benign tumors) on the juxtaepiphyseal regions of enchondral bones. The long term goal of this research project is the complete characterization at the molecular level of the genes which are responsible for the phenotypes associated with the Langer-Giedion syndrome and the related syndromes hereditary multiple exostoses and trichorhinophalangeal syndrome type 1. This application encompasses the following three specific aims which are directed at our long term goal. First is to isolate and characterize the genes located in the LGS region including TRPSI and any genes that may be involved in normal mental function. Second, isolate and characterize the gene for EXT2 present on chromosome 11 and look for clues as to how its function is related to EXT1. Third, use the mouse as a model system to analyze the role of EXT1 in bone development and tumorigenesis. Characterize the temporal and spatial pattern of EXT1 expression in the mouse using both RNA blot and in situ hybridization techniques determine the role this gene plays in vivo by analyzing mice with a null mutation in the EXT1 gene. The genes involved in the pathology of Langer-Giedion syndrome are likely to be involved in the normal development of bone and connective tissues and of normal mental capabilities. Understanding the functions of these genes may give us insights into these important developmental processes as well as tumor suppression. Molecular analysis of the Langer-Giedion genes will be an essential step towards a detailed understanding of their functions.