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

Abstract

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.

Molecular characterization of deletion breakpoints in adults with 22q11 deletion syndrome

“…Previously published analyses of the proximal breakpoint have been reported between D22S427 and D22S1638 (~400 kb) (Carlson et al 1997;Kurahashi et al 1997;Vittorini et al 2001). However, the location of the telomeric breakpoint has not been conclusively mapped to one location as published studies implicate slightly different regions: D22S935/936 to D22S1709 (~850 Kb) (Carlson et al 1997), D22S935 to D22S938 (~930 Kb) (Kurahashi et al 1997), and D22S1709 to D22S306/308 (~1.1 Mb) (Vittorini et al 2001). Our results are consistent with another study (Jacquet et al 2002) that used a similar qPCR method with slightly less map coverage (n = 23 probes) in 14 patients with 22q11DS.…”

“…Consistent with most studies of 22q11DS that primarily examined major congenital features (Carlson et al 1997;Kurahashi et al 1997;Saitta et al 2004) we found no evidence for genotype-phenotype associations using a schizophrenia phenotype. Our study, like others with few individuals having any single variant deletion, had insufficient power to detect modest effects of deletion extent.…”

“…Our results showed that the majority of the 44 adults with 22q11DS studied shared a common 3.1 Mb hemizygous deletion of 22q11.2, consistent with the literature (Carlson et al 1997;Kurahashi et al 1997;Lindsay et al 1995;Saitta et al 2004). We refined the proximal breakpoint location to a ~250 Kb segment between USP18 and PRODH, and the distal breakpoint to a ~350 Kb segment between D22S936 and HIC2.…”

“…1), with the exception of the short nested 1.4 Mb deletion (ID 24), which had a distal breakpoint in a ~100 Kb segment between ARVCF and RANBP1. This deletion appears similar to the 1.5 Mb deletion previously described (Carlson et al 1997;Kurahashi et al 1997;Lindsay et al 1995;Saitta et al 2004), with breakpoints between D22S933 and ZNF74 (~706 Kb). The distal deletion breakpoint of these proximal nested deletions is commonly believed to be in LCR-B (Saitta et al 2004), although this would not appear to be the case for the 1.4 Mb deletion we found (Fig.…”

“…In other microdeletion syndromes such as Williams syndrome, some aspects of the phenotype appear related to the length of the deletion (Stock et al 2003). In contrast, most studies of 22q11DS have found no evidence for such an association (Carlson et al 1997;Kurahashi et al 1997;Lindsay et al 1995;Saitta et al 2004). Some recent studies have reported possible genotype-phenotype correlations, but these were based on small samples of patients with uncommon deletions and congenital phenotypic features (Bartsch et al 2003;Rauch et al 2005).…”