FISH analysis for apparently simple terminal deletions of the X chromosome: Identification of hidden structural abnormalities

We report on fluorescence in situ hybridization (FISH) analysis in 30 mosai c or nonmosaic females diagnosed as having apparently simple terminal X del etions by standard G-banding analysis. FISH studies for DXZ1, the Xp and Xq telomere regions, and the whole X chromosome painting were carried out for the 30 females, indicating rearranged X chromosomes with signal patterns d iscordant with terminal deletions in 6 cases: one dic(X)(DXZ1++) chromosome , two der(X)(qtel++) chromosomes, one Xq(qtel+) chromosome, and two der(X)( ptel++) chromosomes. Additional FISH studies were performed for the 6 cases using probes defining 12 loci on the X chromosome, showing large Xp deleti on and small Xp duplication in the dic(X)(DXZ1++) chromosome, partial Xp de letions and partial Xq duplications in the two der(X)(qtel++) chromosomes, an interstitial Xq deletion in the Xq- (qtel+) chromosome, and partial Xq d eletions and partial Xp duplications in the two der(X) (ptel++) chromosomes . Clinical assessment of the 6 cases revealed tall and normal stature in th e two mosaic cases with the der(X)(ptel++) chromosomes that were shown to b e associated with SHOX duplication. The results suggest that unusual X chro mosome rearrangements are often misinterpreted as simple terminal X deletio ns, and that FISH analysis is useful for precise structural determination a nd better genotype-phenotype correlation of the X chromosome aberrations. ( C) 2001 Wiley-Liss, Inc.