Hormonal and molecular genetic findings in 46,XX subjects with sexual ambiguity and testicular differentiation

Abstract

Ten patients were studied who had sexual ambiguity having in common a 46.XX karyotype and testicular tissue. They were aged from one month to 23 years; some of them were followed through puberty. Eight cases were sporadic and two familial. They were divided into two groups according to finding of surgery and histology: 46, XX males with sexual ambiguity and 46 XX true hermaphrodites (TH). They were no differences in phenotypes (except uterus and ovotestis in TH). The endocrinological data were identical in the two groups: testosterone levels were in the normal range during puberty, then decreased in adulthood. Gonadotrophins were above the normal range at mid-puberty. Gonadal biopsies, regardless of the ovarian part of the ovotestis, were identical in two groups, i.e., normal in the youngest patients, then spermatogonia disappeared afterwards and dysgenesis became obvious. In one case, the ovarian zone of the ovotestis was only detected on serial cuts after gonadectomy. Southern blots displayed the presence of Y specific material in tow cases (PABY-SRY-PO.9). Otherwise, in all other patients, there was the lack of any Y sequences without any differences between the two groups. These data suggests that 46, XX males with sexual ambiguity and 46 XX true hermaphrodites may be alternative expressions of two genetic defects: one, a minimal interchange between Yp and Xp, another, a mutation of an autosomal testis determining factor for the patients without Y detectable material.