An atypical Turner syndrome patient with ring X chromosome mosaicism

Small marker chromosomes (SMC) associated with severe Turner syndrome (TS) variants often represent reduced X chromosomes lacking the X inactivation center (XIC), perturbed dosage compensation, and unbalanced gene expression. A TS patient with mental retardation (MR), unusually short stature, facial and limb malformations, and karyotypic mosaicism involving SMCs is described. Cytogenetic and fluorescence in situ hybridization (FISH) studies of blood and lymphoblastoid cells showed that the SMC was X-chromosome derived, contained a functional centromere, and had ring formation. Karyotypes of 45/46,X,r(X) in blood cells and 45,X/46,-XX/46,X,r(X)/47,X,r(X), + r(X) in fibroblasts were found. Late-replication of the SMC was inconclusive, but the X inactivation specific transcript (XIST) locus within XIC was demonstrated by fluorescent in situ hybridization (FISH). Mechanisms are reviewed that can account for our patient's unusual TS phenotype.