Usefulness and limitations of FISH to characterize partially cryptic complex chromosome rearrangements

Interpretation of a complex chromosome rearrangement (CCR) using only G-ban d analysis is difficult and potentially inaccurate. We present two patients with de novo, partially cryptic, CCRs that illustrate both the value and l imitations of using fluorescence in situ hybridization (FISH) whole chromos ome paint probes to characterize these types of rearrangements, In a patien t referred because of features of Townes-Brocks syndrome, G-band analysis r evealed an unbalanced CCR involving 3 chromosomes (2,11 and 16) and at leas t 4 breakpoints. A more complex rearrangement involving two cryptic inserti ons and at least 6 breakpoints, however, was detected using whole chromosom e paint probes specific for the 3 chromosomes involved in the rearrangement . In this case, FISH studies were essential for accurate characterization o f this patient's rearrangement. In a second patient, G-band analysis reveal ed that a 12-year-old male with obesity, small genitalia, attention deficit disorder, learning disabilities, and behavior problems, carried a CCR invo lving 4 chromosomes (3, 5, 10 and 13) with 6 breakpoints, This rearrangemen t seemed unbalanced, with missing terminal 3p26.2-pter material. Our G-band interpretation of this karyotype was confirmed by FISH using whole chromos ome paint probes specific for the involved chromosomes. Although no evidenc e of the "missing" 3pter material was observed using a chromosome 3 paint, FISH analysis using a chromosome 3p unique telomere probe identified telome ric 3p material on the distal long arm of the derivative 10 chromosome. Thi s case illustrates the limited value of painting probes to detect small rea rrangements, especially those involving terminal chromosome regions, (C) 20 00 Wiley-Liss, Inc.