22q11.2 is a common breakpoint to multiple congenital reciprocal translocations about 20% of which have cryptic deletions
Apparently balanced structural chromosome rearrangements especially balanced translocations are common in the general population. The constitutional t(11;22)(q23;q11.2) is the most common recurrent non-Robertsonian translocation in humans mediated by paralogous low-copy repeats. In earlier reports of t(11;22), a common breakpoint on 22q11.2 was mapped within a 400 kbp interval. In our 15 carriers of the t(11;22), the breakpoint on 22q11.2 was localized between AC007663 and AC007731, which is consistent with the published results. To determine whether the same interval was involved with other balanced translocations except for the t(11;22), 12 balanced-translocation carriers including t(1;22), t(2;22), t(3;22), t(5;22), t(10;22), t(12;22), t(15;22), t(16;22), and t(17;22) were further characterized with fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes (BAC). We used twenty-two home-brewed BACs, with an average size of 80 Kbp. Unexpectedly, the same common breakpoint on 22q11.2 was observed in nine cases (75%). Among these nine cases, seven seemed to be balanced-translocation and two revealed a 3 Mbp deletion centric to the common breakpoint. The other three cases had a breakpoint either at AC016027 (2.5 Mbp centric of the common breakpoint) or at AP000356.1 (4.1 Mbp telomeric of the common breakpoint). Three of all cases (25%) had a cryptic deletion. The translocation-specific junction fragments will be further characterized using multiplex ligation-dependent probe amplification (MLPA) technique. The involvement of palindromic AT-rich repeats on chromosome 22q11.2 in these rearrangements and the mechanisms for generating balanced and unbalanced translocations are proposed.