Uniparental and functional X disomy in Turner syndrome patients with unexplained mental retardation and X derived marker chromosomes

We analysed parental origin and X inactivation status of X derived marker (mar(X)) or ring X (r(X)) chromosomes in six Turner syndrome patients. Two of these patients had mental retardation of unknown cause in addition to the usual Turner syndrome phenotype. By FISH analysis, the mar(X)/r(X) chromosomes of all patients retained the X centromere and the XIST locus at Xq13.2. By polymorphic marker analysis, both patients with mental retardation were shown to have uniparental X disomy while the others had both a maternal and paternal contribution of X chromosomes. By RT-PCR analysis and the androgen receptor assay, it was shown that in one of these mentally retarded patients, the XIST on the mar(X) was not transcribed and consequently the mar(X) was not inactivated, leading to functional disomy X. In the other patient, the XIST was transcribed but the r(X) appeared to be active by the androgen receptor assay. Our results suggest that uniparental disomy X may not be uncommon in mentally retarded patients with Turner syndrome. Functional disomy X seems to be the cause of mental retardation in these patients, although the underlying molecular basis could be diverse. In addition, even without unusual dysmorphic features, Turner syndrome patients with unexplained mental retardation need to be investigated for possible mosaicism including these mar(X)/r(X) chromosomes.