PATHOGENETICS OF 45,X 46,XY GONADAL MOSAICISM

Five patients with 45,X/46,XY mosaicism ranging from 8% to 66% of 46,X Y lymphocytes in the peripheral blood were studied. Their age when chr omosome studies were performed ranged from a few days to 37 yr. The ph enotypic presentations were two females with gonadal dysgenesis and Tu rner syndrome features (cases 1 and 2), two males with ambiguous genit alia and mixed gonadal dysgenesis (cases 3 and 4), and an infertile ma le with an atrophic testis (case 5). Fluorescence in situ hybridizatio n (FISH) using dual-color X and Y probes on paraffin-embedded sections of the gonads was performed to assess mosaicism. A mosaic cell line w ith 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 th an the ovary had. However, the highest ratio of cells with a Y chromos ome was in the atrophic testis of the infertile male (case 5). The dis tribution of mosaic clones in the different gonadal cell types was exa mined. Both females (cases 1 and 2) with dysgenetic gonads had scant o varian stroma and nests of Leydig or hilus cells. In FISH studies, the coelomic epithelial cells were predominantly 46,XY; in comparison, th e 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 simil ar to 21 % of Sertoli cells and similar to 14% of Leydig cells. The in fertile male had an atrophic testis with interstitial hyperplasia (cas e 5). His testis contained Sertoli cells but no evidence of spermatoge nesis. FISH detected a Y signal in about 50-60% of the Sertoli and Ley dig cells.