CAT EYE SYNDROME CHROMOSOME BREAKPOINT CLUSTERING - IDENTIFICATION OF2 INTERVALS ALSO ASSOCIATED WITH 22Q11 DELETION SYNDROME BREAKPOINTS

The supernumerary cat eye syndrome (CES) chromosome is dicentric, cont aining two copies of 22pter-->q11.2. We have found that the duplicatio n breakpoints are clustered in two intervals. The more proximal, most common interval is the 450-650 kb region between D22S427 and D22S36, w hich corresponds to the proximal deletion breakpoint interval found in the 22q11 deletion syndrome (DiGeorge/velocardiofacial syndrome). The more distal duplication breakpoint interval falls between CRKL and D2 2S112, which overlaps with the common distal deletion interval of the 22q11 deletion syndrome. We have therefore classified CES chromosomes into two types based on the location of the two breakpoints required t o generate them. The smaller type I CES chromosomes are symmetrical, w ith both breakpoints located within the proximal interval. The larger type II CES chromosomes are either asymmetrical, with one breakpoint l ocated in each of the two intervals, or symmetrical, with both breakpo ints located in the distal interval. The co-localization of the breakp oints of these different syndromes, plus the presence of low-copy repe ats adjacent to each interval, suggests the existence of several speci fic regions of chromosomal instability in 22q11.2 which are involved i n the production of both deletions and duplications. Since the phenoty pe associated with, the larger duplication does not appear to be more severe than that of the smaller duplication, determination of the type of CES chromosome does not currently have prognostic value.