MOLECULAR ANALYSIS OF LANGER-GIEDION SYNDROME

Langer-Giedio 综合征的分子分析

• 批准号: 2673650
• 负责人: DAN E WELLS
• 金额: $ 19.8万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2673650
• 关键词: Mus musculus; achondroplasia; bone development; carcinogenesis; chromosome deletion; congenital skeletal disorder; cytogenetics; developmental genetics; family genetics; gene expression; gene rearrangement; gene targeting; genetic polymorphism; genetically modified animals; human genetic material tag; human tissue; in situ hybridization; linkage mapping; molecular pathology; northern blottings; nucleic acid sequence; phenotype; polymerase chain reaction; pulsed field gel electrophoresis; southern blotting

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.

描述（改编自研究者摘要）：Langer-Giedion 综合征的特点是手部有圆锥形骨骺，多发性骨骺 软骨外生骨疣、身材矮小和特征性的 颅面畸形、智力低下。 临床特点 Langer-Giedion 综合征的症状与 I 型毛鼻指综合征，但后者不 包括多发性外生骨疣，很少包括智力低下。 这 LGS 中发现的外生骨疣与遗传性外生骨疣本质上相同 多发性外生骨疣，一种常染色体显性遗传疾病，其特征为 骨骺旁多发性软骨帽外生骨疣（良性肿瘤） 软骨骨区域。 该研究项目的长期目标是 基因的分子水平的完整表征 负责与 Langer-Giedion 综合征相关的表型 以及相关的遗传性多发性外生骨疣综合征 1 型毛鼻指综合征。本申请涵盖 遵循针对我们长期目标的三个具体目标。 首先是分离和表征位于 LGS 区域的基因 包括 TRPSI 和任何可能涉及正常心理的基因 功能。 其次，分离并表征 EXT2 存在的基因 11 号染色体并寻找其功能与 EXT1 有何关系的线索。 三、以小鼠为模型系统分析EXT1在骨中的作用 发育和肿瘤发生。 表征时间和空间 使用 RNA 印迹和原位分析小鼠中 EXT1 的表达模式 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 基因无效突变的小鼠。 涉及的基因 Langer-Giedion 综合征的病理学可能涉及 骨骼和结缔组织以及正常智力的正常发育 能力。 了解这些基因的功能可能会给我们带来帮助 深入了解这些重要的发育过程以及肿瘤 抑制。 Langer-Giedion 基因的分子分析将是 详细了解其功能的重要一步。

项目成果

Alignment of physical and genetic maps of human 8q23-qter using somatic cell hybrid mapping panel.

使用体细胞混合作图面板对人类 8q23-qter 的物理和遗传图谱进行比对。

• DOI: 10.1007/bf02290684
• 发表时间: 1994
• 期刊: Somatic cell and molecular genetics
• 作者: Parrish,JE;Wang,Y;Wagner,MJ;Wells,DE
• 通讯作者: Wells,DE

Assignment of fragile site 8E (FRA8E) to human chromosome band 8q24.11 adjacent to the hereditary multiple exostoses 1 gene and two overlapping Langer-Giedion syndrome deletion endpoints.

将脆弱位点 8E (FRA8E) 分配给人类染色体带 8q24.11，邻近遗传性多发性外生骨疣 1 基因和两个重叠的 Langer-Giedion 综合征缺失端点。

• DOI: 10.1159/000134628
• 发表时间: 1997
• 期刊: Cytogenetics and cell genetics
• 作者: Hill,A;Harada,Y;Takahashi,E;Hou,J;Wagner,MJ;Wells,DE
• 通讯作者: Wells,DE

Identification of the Xenopus laevis cDNA for EXT1: a phylogenetic perspective.

非洲爪蟾 EXT1 cDNA 的鉴定：系统发育的角度。

• DOI: 10.1080/10425170290029990
• 发表时间: 2002
• 期刊: DNA sequence : the journal of DNA sequencing and mapping
• 作者: Hill,AL;Brown,N;Hill,MS;Wells,DE
• 通讯作者: Wells,DE

An integrated physical map of 8q22-q24: use in positional cloning and deletion analysis of Langer-Giedion syndrome.

8q22-q24 的综合物理图谱：用于 Langer-Giedion 综合征的位置克隆和缺失分析。

• DOI: 10.1006/geno.2000.6438
• 发表时间: 2001
• 期刊: Genomics.
• 作者: Hilton,MJ;Gutierrez,L;Zhang,L;Moreno,PA;Reddy,M;Brown,N;Tan,Y;Hill,A;Wells,DE
• 通讯作者: Wells,DE

An integrated physical map covering 25 cM of human chromosome 8.

覆盖人​​类 8 号染色体 25 cM 的综合物理图。

• DOI: 10.1006/geno.1996.0084
• 发表时间: 1996
• 期刊: Genomics.
• 作者: Chen,W;Hou,J;Wagner,MJ;Wells,DE
• 通讯作者: Wells,DE