OBJECTIVE We explored the possibility of a genetic anomaly in the sex determining region of the Y chromosome, SRY gene, known to be equated to the testis determining region.PATIENTS Four patients with bilateral congenital anorchia, absence of testicular tissue, elevated FSH and a lack of testosterone response to human chorionic gonadotrophin stimulation tests were studied.MEASUREMENTS Amplification by polymerase chain reaction of the SRY gene and direct double stranded DNA sequencing were performed with the same primers.RESULTS The expected 648 basepairs band of SRY was detected in the four DNA samples from patients with bilateral congenital anorchia. Direct sequencing did not show any difference with the previous published sequence.CONCLUSIONS These data suggest that, in the four patients, bilateral congenital anorchia is not related to an anomaly of the opening reading frame sequence of the SRY gene.

Introduction. Genital abnormalities such as micropenis, hypospadias, and cryptorchidism have been reported in Klinefelter's syndrome. We studied the biochemical and molecular characteristics of the androgen receptor (AR) in 5 patients with Klinefelter's syndrome (47,XXY) and a severe micropenis. Patients. Clinical, biochemical and molecular data are reported in the table below.Methods. AR binding capacity was studied on genital skin fibroblasis and SSCP analyses were performed in exons 4-8 in order o delect any alterations within the androgen binding domain of the AR gene.Results. The 5 patients exhibited a decreased amount of AR (mean = 258±36 fmol/mg DNA vs 650±200 fmol/mg DNA for N) compatible with the diagnosis of PAIS while the Kd of the AR were in normal range (mean = 0.7±0.2 nM vs 0.6±0.3 nM for N). Furthermore, no band shifts, characteristic of point mutations, were found by PCR coupled with SSCP. Known AR mutated exons detecled by SSCP were used as control.Discussion. AR gene mutations have been reported in patients with partial androgen insensitivity syndrome and diminished receptor binding capacity. These mutations have been located within the androgen-binding domain. In these patients with Klinefelter's syndrome and severe micropenis, the decrease of AR binding capacity is in favor of PAIS. However, a diminution of AR gene expression responsible for the low amount of AR cannot be ruled out.

In Turner patients, the presence of a Y chromosome or derivative Y is correlated with the risk of gonadoblastoma induction. "Marker" chromosomes originating from Y, may not show characteristic fluorescence and then be very difficult to identify by conventional cytogenetic techniques, although they still predispose the patients to gonadal tumors. Using polymerase chain reaction of the gene from the sex-determining region of the Y chromosome, we screened 40 Turner patients (thirty seven 45X and three 45X,46XX) for the presence of Y chromosomal DNA. We were able to identify karyotypically unrecognized Y chromosome material in 1 patient out of the 40 studied. In this patient mild clinical and biological hyperandrogenism was observed. Reliability of our technique was ascertained by the detection of the expected 648 base pairs amplified DNA fragment in all normal male controls as well as in 3 Turner patients with confirmed 45X,46XY mosaicism. Despite the low frequency of unrecognized Y chromosome material (1 case over 40 in our experience), our data suggest that polymerase chain reaction of the gene from the sex-determining region of the Y chromosome is worthy of being performed in Turner patients considering the potential risk of the presence of a Y chromosome.

Hyperandrogenism in adolescent girls can be a troubling problem because of the difficulty in establishing a diagnosis and in prescribing appropriate therapy. Androgen excess in adolescent patients encompasses a spectrum of clinical presentations, including acne, hirsutism, oligomenorrhea, amenorrhea, virilism, and ovarian cysts. Androgen excess is a clinical and chemical feature of idiopathic hirsutism, late-onset forms of congenital adrenal hyperplasia, and polycystic ovarian disease; in some cases, functional hyperandrogenism is discussed. We recommend screening for hyperandrogenism by measuring blood levels of testosterone, dehydroepiandrosterone sulfate, and delta 4-androstenedione, while others propose a first dexamethasone suppression test for evaluation of free testosterone, dehydroepiandrosterone sulfate, and cortisol. Treatment will be chosen according to particular symptoms such as acne, hirsutism, obesity, or oligomenorrhea.