Wadey R, Daw S, Taylor C, Atif U, Kamath S, Halford S, O'Donnell H, Wilson D, Goodship J, Burn J
Molecular Medicine Unit, Institute of Child Health, London, UK.
Hum Mol Genet. 1995 Jun;4(6):1027-33. doi: 10.1093/hmg/4.6.1027.
Deletions within 22q11 have been associated with a wide variety of birth defects embraced by the acronym CATCH22 and including the DiGeorge syndrome, Shprintzen syndrome (velocardiofacial syndrome) and congenital heart disease. It is not known how many genes contribute to this phenotype. Previous studies have shown that a balanced translocation disrupts sequences within the shortest region of deletion overlap for DiGeorge syndrome. A P1 clone was isolated which spans this breakpoint and used to isolate a cDNA encoding a transmembrane protein expressed in a wide variety of tissues. This gene (called IDD) is not disrupted by the translocation, but maps within 10 kb of the breakpoint. Mutation analysis of five affected cases with no previously identified chromosome 22 deletion was negative, but a potential protein polymorphism was discovered. No deletions or rearrangements were detected in these patients following analysis with markers closely flanking the breakpoint, data which emphasize that large (i.e. over 1 Mb) interstitial deletions are the rule in DiGeorge syndrome. The proximity of IDD to the balanced translocation breakpoint and its position within the shortest region of deletion overlap indicate that this gene may have a role, along with other genes, in the CATCH22 haploinsufficiency syndromes.
22q11区域内的缺失与一系列由首字母缩写词CATCH22涵盖的出生缺陷相关，包括迪格奥尔格综合征、施普林曾综合征（心脏颜面综合征）和先天性心脏病。目前尚不清楚有多少基因导致了这种表型。先前的研究表明，一种平衡易位破坏了迪格奥尔格综合征缺失重叠最短区域内的序列。分离出了一个跨越该断点的P1克隆，并用于分离一个编码在多种组织中表达的跨膜蛋白的cDNA。这个基因（称为IDD）没有被易位破坏，但定位于断点的10 kb范围内。对5例先前未发现22号染色体缺失的受累病例进行的突变分析为阴性，但发现了一种潜在的蛋白质多态性。在用紧密位于断点两侧的标记进行分析后，在这些患者中未检测到缺失或重排，这些数据强调大的（即超过1 Mb）间质性缺失是迪格奥尔格综合征的常见情况。IDD与平衡易位断点的接近程度及其在缺失重叠最短区域内的位置表明，该基因可能与其他基因一起，在CATCH22单倍剂量不足综合征中发挥作用。
