Molecular genetics of Digeorge syndrome and related disorders

患有先天性畸形综合征的患者，如DiGeorge综合征、圆锥干畸形面部综合征，通常在22q11处有缺失。缩写Catch22现在被用来描述这种综合征，因为它们被认为是由一个连续的基因综合征组成的。虽然已经定位了几个在该缺失中的基因，但它们是否在该综合征的发生发展中起作用尚不清楚。为了定位Catch22关键区，利用散布在缺失区域的多个基因组克隆构建了100例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-基因相关分析表明，Catch22不是一种邻接基因综合征。多数患者存在常见的大片段缺失，提示存在易引起缺失的特征重复序列。我们还对常见大缺失的边界进行了局部化，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.