Assessment of sex chromosome composition using fluorescent in situ hybridization as an adjunct to GTG-banding

Fluorescent in situ hybridization (FISH) using dual color X chromosome- and Y chromosome-specific probes was employed to assess further the sex chromosome copy number in cells of a phenotypic female patient with hypergonadotropic hypogonadism, primary amenorrhea and growth retardation. The GTG-banding analysis of peripheral blood lymphocytes had revealed the presence of predominantly 46,XY cells. A FISH analysis, undertaken to assess further the contribution of a minor cell line, yielded frequencies of 87% cells with the 46,XY constitution and 9% with the 45,X constitution. To establish unequivocally the presence of mosaicism, a skin biopsy was obtained for fibroblast culture, which further corroborated the results of the peripheral blood study. Fluorescent in situ hybridization analysis revealed 74% of the cells to be 46,XY and 12% to be 45,X. The unequivocal presence of XY cells puts the patient at risk for neoplastic transformation of the gonads. Laparoscopy and surgical removal of the patient's presumptive streak gonads were therefore undertaken. Cytogenetic results derived from the gonadal tissues further strengthened findings of previous cytogenetic analyses. It is our experience that FISH is a useful adjunct to established cytogenetic techniques in the management and monitoring of patients similar to the proband described in this study.