Molecular analysis of the endpoint of the common large deletion in catch22

CATCH22 patients are known to show marked phenotipic variability, although the extents of 22ql 1 deletion are uniform. It is suggested that at both ends of the deletion there lies region specific repetitive sequence prone to deletion. We firstly analyzed YAC y966A8 which should contain the proximal end, resulting that critical region is revealed to be deleted in the YAC. Then, y849E9 which should contain the distal end was subcloned into cosmids and analyzed by FISH and Southern hybridization. Approximately half of the cosmids were single copy and located out of the common large deletion. The other half were found to contain 22ql 1 specific multicopy sequences. FISH analysis on various translocated chromosomes showed that their homologous regions are located near the proximal end. It is suggested that these 22ql 1 specific repetitive sequences are related to development of the common large deletion. However, no cosmids showed apparent rearranged bands in patients with deletion. In this region, we identified a VNTR whose homologous region is also located near the proximal end. Detailed analysis of the vicinity of the VNTR revealed that some of patients have rearrangement in the VNTR. It is strongly suggested that this VNTR should be related to development of some types of CATCH22 deletion.