RING CHROMOSOME-X IN A CHILD WITH MANIFESTATIONS OF KABUKI-SYNDROME

A female patient with the karyotype 45, X/46, X,r(X)(p11.2 q13) and se vere developmental delay, prominent fingertip pads, long palpebral fis sures, short stature, and history of hypotonia had a phenotype reminis cent of Kabuki syndrome. We hypothesized that overexpression of X chro mosome-derived sequences might be associated with the Kabuki-like phen otype observed, The nature and parental origin of this small-ring X we re ascertained using a combination of genotyping with microsatellite m arkers and quantitative Southern blotting. PCR-based genotyping demons trated heterozygosity at X-linked loci SBMA (Xq11-q12) and DXS227 (Xq1 3.1). Hemizygosity was observed at several loci: DMD STR-49 (Xp21.2), DXS1003 (Xp11.23), DXS988 (Xp11.21), DXS101 (Xq21.3), FMR-1 (Xq27.3), and DXYS64 (Xq28). This ring X chromosome is paternally derived since only maternal alleles are inherited at three informative microsatellit e loci, Results of FISH and RT-PCR experiments indicate that the XIST locus is missing in the ring X chromosome and not expressed. These dat a indicated a large deletion of the X chromosome consistent with a sma ll-ring X chromosome with approximate breakpoints near p11.2 and q13, These results are comparable to the observation of others where an aty pically severe phenotype has been associated with the presence of an r (X), or small mar(X). (C) 1997 Wiley-Liss, Inc.