Kabuki syndrome-like features associated with a small ring chromosome X and XIST gene expression

Although clinical features in Kabuki syndrome (KS; Niikawa-Kuroki syndrome) have been well defined, the underlying genetic mechanism still remains unc lear. We report a 9-year-old girl with typical KS-like facial appearance, s keletal and dermatoglyphic abnormalities, severe mental retardation, and gr owth deficiency. In 60 of 100 GTG-banded metaphases from peripheral blood l ymphocytes, a ring chromosome smaller than a G group chromosome was found, which, according to reverse painting, consisted of Xq11.1q13. The proband's karyotype was described as mos45,X/46,X,+r(X). Several loci were analyzed with fluorescence in situ hybridization (FISH) and microsatellite markers r evealing that one r(X) breakpoint mapped proximal to DXS422 (Xp11.21) and t he second mapped distal to XIST gene, between loci DXS128E and DXS441 (Xq13 .2). Uniparental disomy for X and r(X) was excluded and the paternal origin of r(X) was identified. XIST expression was demonstrated by nested reverse transcription polymerase chain reaction (RT-PCR) using primers spanning ex ons 5, 6i, and 6 in RNA prepared from lymphocytes. The observation of XIST expression is in contrast to two other cases in which the XIST gene was eit her not present on r(X) or not expressed. To our knowledge, this is the fir st case of Kabuki-like syndrome manifestations with r(X) and XIST expressio n. (C) 2001 Wiley-Liss, Inc.