Localization by fish of centric fission breakpoints in a de novo trisomy 9p patient with i(9p) and t(9q;11p)

Localization by FISH of centric fusion breakpoints in a de novo trisomy 9p patient with i(9p) and t(9q;11p): In this report we present a 38 year-old, severely mentally retarded female with 9p trisomy due to isochromosome 9p, i(9p), formation and translocation of the long arm of the rearranged chromosome 9 onto the telomere region of the short arm of chromosome 11: karyotype: 46, XX, -9, -11, +i(9p), +der(ll) t(9;11) (q12;p15.5). C-banding showed that the i(9p) was monocentric and that der(11) had an additional C-band at the t(9q;11p) junction. The centric rearrangements were further identified by fluorescence in situ hybridisation (FISH) using a panel of chromosome 9 (peri)centric DNA probes. Analysis with probe pG-Xbal 1/340 (locus D4Z1), detecting the satellite subfamily at the centromeres of chromosomes 4 and 9, revealed small signals at the primary constriction of i(9p) but no signals at the breakpoint junction of the t(9q;11p). Further analysis using respectively chromosome 9 classical satellite probe (locus D9Z1), that consists of beta satellite sequences and pHuR98 probe (locus D9Z3) which detects satellite 3 DNA,localized to the 9qh region, both revealed translocation of these DNA sequences to the breakpoint of the t(9;11) junction. By using a 3' biotinylated oligonucleotide (TTAGGG)(7) probe, no evidence was found for the presence of interstitial telomeric repeats at the t(9q;11p) breakpoint junction indicating that this derivative chromosome is the result of a reciprocal translocation with loss of telomeric regions including terminal 11p15.5-->pter. Our results provide evidence that the misdivision process that occurs on the chromosome 9 centric region results either from breakage in the alphoid DNA arrays or at the junction between alphoid and DNA regions.