Fluorescence in situ hybridisation analysis and ovarian histology of women with Turner syndrome presenting with Y‐chromosomal material: a correlation between oral epithelial cells, lymphocytes and ovarian tissue

摘要

Turner syndrome (TS) affects about one in 2500 newborn girls (Magalini and Magalini 1997). The karyotype 45,X is found in about 25–30 % of the TS women, while sex chromosomal mosaicism occur in about 70 % of cases (Hanson et al. 2001b; Held et al. 1995).One of the features of TS is infertility due to an accelerated rate of atresia of ovarian follicles, in most cases resulting in the development of dysgenetic gonads, known as streak gonads. There is a risk for individuals with dysgenetic gonads and Y-chromosomal material to develop gonadal tumours such as gonadoblastoma.Gonadoblastoma is a tumour composed of both germ cells and sex cord elements that may progress into an invasive dysgerminoma with a severe prognosis or evolve into other forms of malignant germ cell tumours (Scully 1970). Therefore, the streak gonads of TS patients are today routinely removed as soon as possible once Y-chromosomal material has been confirmed. It is thus of outmost importance to be able to detect Y-chromosomal material as early as possible in TS females.In 1987, Page formulated a hypothesis of a gene on the Y chromosome (GBY; GonadoBlastoma locus on Y chromosome) causing gonadoblastoma in the context of a dysgenetic gonad (Page 1987). This putative locus has since then, by deletion mapping, been localised to a region containing the Y-centromere, including parts of Yp and Yq (Salo et al. 1995; Tsuchiya et al. 1995).The Y-chromosomal material in TS individuals is often present in the form of small marker chromosomes, which are difficult to positively identify by routine karyotyping. Furthermore, small markers are frequently missed altogether using this technique, especially if limited numbers of metaphases are evaluated. The use of fluorescence in situ hybridisation (FISH) analysis has been well documented as being effective in detecting and identifying sex chromosome markers (Schwartz et al. 1997).The distribution of Y-chromosomal material in TS patients may vary between different tissues (Petrusevska et al. 1996; Atkins et al. 2000). Since it is believed that gonadoblastoma develops from Y-positive gonadal cells (Page 1987), it is important to investigate how often Y-chromosomal material found in, e.g. lymphocytes, correlates to the presence of Y-material in the gonads. Previous work indicates that the presence, but not necessarily the frequency, of Y-positive nuclei in lymphocytes correlates to that in gonadal cells (Atkins et al. 2000). However, at least one girl with TS features and virilised external genitalia that had Y-chromosomal material in her gonads, but not in her blood, has been reported (Bisat et al. 1993).The aim of this study was to further define the Y-chromosomal fragments and their tissue distribution in twelve TS patients, and to describe the histology of the ovarian tissue of these women. Epithelial cells of the oral mucosa (buccal cells), peripheral blood lymphocytes, as well as sections of gonadal tissue obtained at gonadectomy were studied. The presence or absence of three different loci on the Y chromosome was investigated: the Sex determining Region on the Y chromosome (Yp11.3; SRY probe), the centromere (Ycen; DYZ3 probe) and the heterochromatic region on the long arm (Yq12; DYZ1 probe). SRY was chosen to see if there was any correlation between its level when present and signs of virilisation in the women. Presence of the centromeric region is relevant for the risk of gonadoblastoma development. Breakpoints in the Yq12 region has been reported as a common feature in TS women with structurally abnormal Y chromosomes (Robinson et al. 1999).