Identification of Y chromatin directly in gonadal tissue by fluorescence in situ hybridization (FISH): Significance for Ullrich-Turner syndrome screening in the cytogenetics laboratory

Abstract

The presence of Y chromatin in individuals with Ullrich-Turner syndrome (UTS) confers a risk for gonadoblastoma. In mosaic cases, little is known about Y chromatin distribution in gonads. Fluorescence in situ hybridization (FISH) is a direct approach to assess the extent of Y chromatin mosaicism in gonads. Gonadal tissue from four patients with mosaic karyotypes were analyzed by routine cytogenetics and FISH with X and Y centromere probes. Y chromatin was present in gonads in varying percentages in these patients. The distribution of Y chromatin in gonads of UTS individuals did not completely correlate with that found in blood lymphocytes. The finding of Y chromatin in the blood samples from these patients prompted the development of a screening strategy in our cytogenetics laboratory to detect low-level Y chromatin mosaicism in patients with UTS.

Impact of the Y‐containing cell line on histological differentiation patterns in dysgenetic gonads

“…As in previous studies 7,8,10 we observed no correlation between the degree of mosaicism in PBL and in gonadal cells, nor was the PBL karyotype able to predict the differentiation patterns that had developed in the dysgenetic gonad. Differential growth of the 45,X and 46,XY cell lines in vitro and the selection of a subset of clones for PBL karyotyping cannot be excluded.…”

“…In spite of our increasing knowledge on genes involved in normal sex development, the disturbed gonadal differentiation processes that underlie gonadal dysgenesis (GD) syndromes are less well understood 1–5 . Little is known about the correlations between peripheral blood (PBL) karyotype and/or skin fibroblasts on the one hand, and the gonadal karyotype and morphological differentiation patterns of the gonad on the other 6–11 . Traditionally, in GD, three differentiation patterns have been described: (dysgenetic) testicular tissue, ovarian tissue, and streak gonads.…”

“…It was shown that in the presence of TSPY, areas of gonadal tissue with a low degree of differentiation (UGT) are at highest risk for GB development 12 . The direct exclusion or confirmation of Y chromosomal material in the dysgenetic gonad is more relevant in this context than PBL karyotyping but is technically more difficult 7,10 . Because of the risk for germ cell tumours a prophylactic gonadectomy has been advised in all GD patients 21–24 .…”

“…[1][2][3][4][5] Little is known about the correlations between peripheral blood (PBL) karyotype and/or skin fibroblasts on the one hand, and the gonadal karyotype and morphological differentiation patterns of the gonad on the other. [6][7][8][9][10][11] Traditionally, in GD, three differentiation patterns have been described: (dysgenetic) testicular tissue, ovarian tissue, and streak gonads. Recently, a fourth pattern was recognized, the so-called undifferentiated gonadal tissue (UGT), which consists of germ cells lining up together with Sertoli/granulosa cells to form cord-like structures, or residing without specific organization in a background of stromal cells.…”

Limitations of G-banding Karyotype Analysis with Peripheral Lymphocytes in Diagnosing Mixed Gonadal Dysgenesis

“…Moreover, monozygotic twins with different phenotypes (presumably due to different ratios of mosaicism of gonadal tissue) have been reported (20,21,22). Different levels of mosaicism of karyotype between lymphocytes and gonadal tissues have already been reported (23,24,25). The results of all four cases in this study confirmed that karyotype analysis of the gonad is more consistent with the phenotype of the gonad and external genitalia.…”