Pathogenetics of 45,X/46,XY gonadal mosaicism

Five patients with 45,X/46,XY mosaicism ranging from 8% to 66% of 46, XY lymphocytes in the peripheral blood were studied. Their age when chromosome studies were performed ranged from a few days to 37 yr. The phenotypic presentations were two females with gonadal dysgenesis and Turner syndrome features (cases 1 and 2), two males with ambiguous genitalia and mixed gonadal dysgenesis (cases 3 and 4), and an infertile male with an atrophic testis (case 5). Fluorescence in situ hybridization (FISH) using dual-color X and Y probes on paraffin-embedded sections of the gonads was performed to assess mosaicism. A mosaic cell line with a Y chromosome was present in the streak ovary, dysgenetic gonad, and testis. In the mixed gonadal dysgenesis cases (cases 3 and 4), the testis had a higher percentage (greater than two fold) of XY cells than the ovary had. However, the highest ratio of cells with a Y chromosome was in the atrophic testis of the infertile male (case 5). The distribution of mosaic clones in the different gonadal cell types was examined. Both females (cases 1 and 2) with dysgenetic gonads had scant ovarian stroma and nests of Leydig or hilus cells. In FISH studies, the coelomic epithelial cells were predominantly 46,XY; in comparison, the Leydig and hilus cells had a lower percentage and the ovarian stroma the least number of cells with a Y signal. A mixed gonadal dysgenesis case (case 3) possessed a right testis with an XY complement in approximately 21% of Sertoli cells and approximately 14% of Leydig cells. The infertile male had an atrophic testis with interstitial hyperplasia (case 5). His testis contained Sertoli cells but no evidence of spermatogenesis. FISH detected a Y signal in about 50-60% of the Sertoli and Leydig cells.