Another critical region for deletion of 22q11: a study of 100 patients

Deletions at 22q11.1-q11.2 present with variable manifestations usually referred to as DiGeorge or velo-cardio-facial syndrome. We previously reported that deletions observed in patients with the syndrome can be subgrouped into three types (common large deletion, proximal deletion, and distal deletion) and demonstrated the presence of a second critical region for the syndrome. In order to characterize further the second critical region, a 22q11 deletion map was constructed from the data of 100 patients, using 12 DNA markers scattered in the common large deletion, and then a phenotype-genotype correlation was analyzed. The second critical region was found to correspond to the distal deletion encompassing the HCF2, cHKAD26, and D22S935 loci, and the proximal and distal deletions do not overlap each other. Although it seems that this condition is a contiguous gene syndrome, the phenotype of patients with these two types of deletion was indistinguishable from that of patients with the common large deletion. Thus, it is plausible that several genes located in the two segments corresponding to the two deleted regions are involved in the same developmental pathway or in an extremely long-range position effect.