Molecular genetics of Digeorge syndrome and related disorders

患有几种先天性异常综合征的患者，如DiGeorge综合征、圆锥动脉干异常面部综合征，通常在22 q11处存在缺失。CATCH 22的首字母缩写现在被用于这些综合征，因为它们被认为是由一个连续的基因综合征。虽然几个cDNA已被定位在这个缺失，这是未知的，他们是否发挥作用，在发展中的综合征。为了定位CATCH 22关键区域，使用分散在缺失中的许多基因组克隆构建了100名患者的精细缺失图谱。结果，患者被分为三种类型的缺失：常见的大缺失，近端缺失和远端缺失。我们确定了共同缺失中的两个关键区域，这将为致病基因的鉴定提供重要信息。表型-基因型相关性表明CATCH 22不是一个相邻基因综合征。大多数患者存在常见的大缺失，提示存在易引起缺失的特征性重复序列。我们还定位了常见的大缺失的边界，这将有助于分析缺失断点。

Patients with several congenital anomaly syndrome, such as DiGeorge syndrome, conotruncal anomaly face syndrome, commonly have a deletion at 22q11. The acronym CATCH22 is now used for such syndromes, for they are thought to consist a contiguous gene syndrome. Although several cDNA have been mapped in this deletion, it is unknown whether they play roles in development of the syndrome. In order to localize the CATCH22 critical region, the refined deletion map of the 100 patients have been constructed using many genomic clones scattered in the deletion. As a result, patients were devided into three types of deletion ; common large deletion, proximal deletion, and distal deletioon. We identified two critical regions in the common deletion, which will provide important information for identification of the disease-causing gene. The phenotype-genotype correlation showed that CATCH22 is not a contiguous gene syndrome. Most patients have the common large deletion, suggesting that there lies characteristic repetitive sequences which easily cause the deletion. We also localized the the boundary of the common large deletion, which would be a help for analysis of the deletion breakpoint.