HYPOHIDROTIC ECTODERMAL DYSPLASIA--GENETIC ANALYSIS

描述(改编自申请人的摘要)：急诊医生是 发病机制不明的异质性疾病集合。有必要 已经注意到开发新的分子方法来分析它们，并且 研究人员认为，分子遗传学研究，特别是连锁 分析，将改进他们的分类，生产新的诊断工具， 并最终导致对它们的分子缺陷的识别和对 对正常形态发生过程的理解。调查人员 建议研究两种典型的疾病，XLHED，最常见的ED， 以及Clouston综合征，这是一种多汗性ED，作为一种遗传性 常染色体显性性状。 对于XLHED：研究人员将进行精细的基因图谱研究 该紊乱定位于Xp11.1-Xq21.1区域，以定义 与疾病基因座紧密连锁的多态标记基因座。 近侧翼标记的识别对于两者的准确性是至关重要的 诊断应用程序，以及用于物理映射和克隆 XLHED轨迹。为此，调查人员将对高度 多态(杂合度&70%)的微卫星DNA标记 X染色体的着丝粒周围区域。调查人员将利用 这些标记用于解决存在和出现频率的问题 临床上难以区分的常染色体隐性遗传性遗传病 紊乱，如果不能识别，可能会导致严重的诊断错误。在……里面 此外，最初将对大量无关的男性进行筛查 使用匿名DNA探针，但最终使用表达和保守的 来自该区域的序列，以识别涉及到的亚微观缺失 XLHED轨迹。 Clouston综合征：目前它在人类基因图谱上的位置 未知，将由本地化的两个很大的连锁分析 利用一系列高度多态的基因座(RFLP和 微卫星)分布在所有常染色体上(排除图谱)。 潜在的候选基因或染色体区域将被优先考虑。 一旦建立了联系，将进行精细测绘，以便为 为随后疾病部位周围的物理测绘奠定基础，以及 基因的克隆。

DESCRIPTION (Adapted from the applicant's abstract): The EDs are a heterogeneous collection of disorders of unknown pathogenesis. The need to develop new molecular approaches to their analysis has been noted, and the investigators believe that molecular genetic studies, specifically linkage analysis, will improve their classification, produce new diagnostic tools, and ultimately lead to identification of their molecular defects and to an understanding of the process of normal morphogenesis. The investigators propose to study two prototypic disorders, XLHED, the commonest of the EDs, and the Clouston syndrome, an hidrotic form of ED which is inherited as an autosomal dominant trait. For XLHED: The investigators will perform fine genetic mapping studies of the disorder, localized to Xp11.1-Xq21.1 region, to define the order of closely linked polymorphic marker loci in relation to the disease locus. The identification of close flanking markers is essential for both accurate diagnostic applications, and for the physical mapping and cloning of the XLHED locus. To this end, the investigators will screen for highly polymorphic (heterozygosity >70 percent) microsatellite DNA markers in the pericentromeric region of the X-chromosome. The investigators will utilize these markers to address the question of the existence and frequency of a proposed clinically indistinguishable autosomal recessive form of the disorder, which if unrecognized could cause serious diagnostic errors. In addition, a large number of unrelated males will be screened, initially with anonymous DNA probes, but ultimately with expressed and conserved sequences from the region, to identify sub-microscopic deletions involving the XLHED locus. For the Clouston syndrome: Its position on the human gene map, presently unknown, will be localized by the linkage analysis of two very large kindreds, utilizing a series of highly polymorphic loci (RFLPs and microsatellites) distributed over all autosomes (exclusion mapping). Potential candidate genes or chromosomal regions will be given priority. Once linkage is established, fine mapping will be performed, to lay the groundwork for subsequent physical mapping around the disease locus, and cloning of the gene.