MOLECULAR AND GENETIC ANALYSIS OF THE EEC SYNDROME

描述（改编自研究者摘要）：外胚层 发育不良包括具有发育异常的疾病， 外胚层组织主要是头发、皮肤、牙齿和指甲。 许多形式的 这种疾病与其他类型的发育障碍一起出现， 一种常见的基因组变异 一种形式，EEC，涉及个人 有外胚层发育不良缺指和腭裂的人 这个实验室和其他人以前的工作已经绘制了一种形式的 缺指（趾）畸形与人类染色体7 q21 -22的同源性。 几个有EEC的家庭也 显示这一区域的染色体异常 因此，校长 研究人员提出，人类基因组的这一区域包含了 导致了这些发育障碍 YAC/粘粒/噬菌体重叠群 在7号染色体的这一区域， 几个候选EEC基因。 在本申请中，提出研究以 通过染色体的分子分析进一步细化EEC基因座 散发性和家族性EEC患者的7 q21 -22靶区域。 完成 为此，研究者将通过PFGE寻找亚显微缺失 南方分析 同时，溶液混合技术 捕获将用于从靶区域分离候选EEC基因。 然后对患者材料进行突变和表达改变的筛选 以及通过SSCP分析寻找这些基因的突变和缺失。 通过多态性mRNA标记的一个等位基因的表达。 最后，耐心 将继续从散发性和家族性EEC中收集样本 患者支持这些正在进行的研究。 此存储库将扩展 包括其他多表型疾病，如Rapp-Hodgkin和拉德 其中也包括ED。然后将确定EEC中的标记物是否 关键区域与其他类型的ED相关 家庭 这些拟议的研究提供了一个独特的机会， 表征负责几个充分表征的人类 发育障碍 此外，了解的职能， 这些基因最终将使研究的分子基础， 降低的表达率和可变的表达率，对遗传 许多遗传性疾病的常见现象。 最后，确定 与EEC相关的各种出生缺陷之间的关系将 允许对患有这种疾病的人进行准确的遗传咨询。

DESCRIPTION (Adapted from investigator's Abstract): The ectodermal dysplasias consist of diseases with developmental abnormalities of ectodermal tissue primarily the hair, skin, teeth, and nails. Many forms of this disease present with other types of developmental disorders suggesting a common genomic alteration among them. One form, EEC, involves individuals who show evidence of ectodermal dysplasia, ectrodactyly and cleft palate. Previous work from this laboratory and others have mapped a form of ectrodactyly to human chromosome 7q21-22. Several families with EEC also show chromosomal abnormalities in this region. Thus, the Principal Investigator proposes that this area of the human genome contains the genes responsible for these developmental disorders. A YAC/cosmid/phage contig across this region of chromosome 7 has been developed and used to identify several candidate EEC genes. In this application, studies are proposed to further refine the EEC locus by a molecular analysis of the chromosome 7q21-22 target region in sporadic and familial EEC patients. To accomplish this aim, the investigator will look for submicroscopic deletions by PFGE and Southern analyses. At the same time, the technique of solution hybrid capture will be used to isolate candidate EEC genes from the target region. Patient material will then be screened for mutations and altered expression as well as look for mutations in these genes by SSCP analysis and loss of expression of one allele by polymorphic mRNA markers. Finally, patient samples will continue to be collected from sporadic and familial EEC patients to support these ongoing studies. This repository will be expanded to include other multiple phenotype disorders such as Rapp-Hodgkin and LADD which also include ED. It will then be determined if markers in the EEC critical region demonstrate linkage to these other types of ED-related families. These proposed studies offer a unique opportunity to isolate and characterize genes responsible for several well-characterized human developmental disorders. Furthermore, an understanding of the functions of these genes will eventually allow investigation of the molecular bases of reduced penetrance and variable expressivity, poorly understood genetic phenomena common to many inherited diseases. Finally, the determination of the relationship among the various birth defects associated with EEC will allow accurate genetic counseling to individuals with this disorder.