Pigmentary mosaicism in hypomelanosis of Ito - Further evidence for functional disomy of Xp

We report on a female with mental and motor retardation, facial dysmorphism , abnormal pigmentation reminiscent to hypomelanosis of Ito (HI), and karyo typic mosaicism involving a small supernumerary marker chromosome. The mark er chromosome was defined by fluorescence in situ hybridisation (FISH) as a ring X chromosome with breakpoints in the juxtacentromeric region. FISH an alysis showed that the ring does not include the XIST locus at the X-inacti vation centre and, therefore, may not be subject to X inactivation. X-inact ivation studies with the HUMARA (human androgen receptor) and FMR1 assay sh owed a skewed X-inactivation pattern (85:15) with preferential inactivation of the paternal X chromosome. These results are discussed with respect to the role of functional disomy of Xp in the pathogenesis of HI.