ABSTRACT
46,XX subjects carrying the testis determining SRY gene usually have a completely male phenotype. In this study, five very rare cases of SRY carrying subjects (two XX males and three XX true hermaphrodites) with various degrees of incomplete masculinisation were analysed in order to elucidate the cause of sexual ambiguity despite the presence of the SRY gene. PCR amplification of 20 Y chromosome specific sequences showed the Yp fragment to be much longer in XX males than in true hermaphrodites. FISH analysis combined with RBG banding of metaphase chromosomes of four patients showed that in all three true hermaphrodites and in one XX male the Yp fragment was translocated onto a late replicating inactive X chromosome in over 90% of their blood lymphocytes. However, in a control classical XX male with no ambiguous features, the Yp fragment (significantly shorter than in the XX male with sexual ambiguity and only slightly longer than in XX hermaphrodites) was translocated onto the active X chromosome in over 90% of cells. These studies strongly indicate that inactivation on the X chromosome spreading into a translocated Yp fragment could be the major mechanism causing a sexually ambiguous phenotype in XX (SRY+) subjects.
Subject(s)
DNA-Binding Proteins/genetics , Disorders of Sex Development , Dosage Compensation, Genetic , Nuclear Proteins , Sex Determination Processes , Transcription Factors , X Chromosome/genetics , Base Sequence , DNA Primers/genetics , Disorders of Sex Development/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Male , Phenotype , Sex-Determining Region Y Protein , Translocation, Genetic , Y Chromosome/geneticsABSTRACT
The excretory patterns of urinary steroids determined by capillary gas chromatography in 11 children (aged 0.8-16.5 years) with adrenocortical tumors were established. In 8 patients the predominant clinical feature was virilization, in 3 others, Cushing's syndrome. In 5 patients (3 carcinoma, 2 adenoma) very high excretion of 3 beta-hydroxy-5-ene steroids was observed. In 2 others (adenomas) only moderately elevated excretion of 11 beta-hydroxyandrosterone was found. In 1 patient (adenoma) pregnanediol dominated in the steroid profile, accompanied by moderately elevated 3 beta-hydroxy-5-ene steroids. Out of 3 Cushingoid patients (1 carcinoma, 2 adenomas), 1 presented an atypical urinary steroid pattern for hypercortisolemia, without 5 alpha-reductase and 11 beta-hydroxysteroid dehydrogenase deficiencies. Neither the urinary steroid pattern nor tumor size alone were reliable indicators of tumor malignancy, as evaluated by a pathological examination and subsequent metastasis-free survival.
