Testing for sex chromosome mosaicism in Turner syndrome

Ullrich–Turner syndrome (UTS) is frequently associated with chromosomal mosaicism. Conventional cytogenetic studies identify sex chromosome mosaicism in approximately 55% of patients. Roughly 2% of UTS patients who are mosaic exhibit a cell population with 46,XY or a structural rearrangement of the Y chromosome. Such patients are at an increased risk of gonadoblastoma and occasionally more clinically significant gonadal tumors. For UTS patients with a monosomy X karyotype result, we developed and validated a FISH assay to identify low level mosaicism for an XY or XX cell population, or an X or Y structural rearrangement. We have tested 44 patients with monosomy X for sex chromosomal mosaicism using FISH. A second cell line was identified in 10 patients (23%), 6 with X/XX, 1 X/i(X), and 3 X/dic(X). None of the patients studied thus far with FISH have exhibited a Y-chromosome cell population. FISH as an adjunct to karyotype analysis is useful to identify sex chromosome mosaicism in UTS patients, and has increased the rate of identification of mosaicism from 55% to 67%.