1/5. Point mutations detected in the androgen receptor gene of three men with partial androgen insensitivity syndrome.OBJECTIVE: Determine the sequence of the androgen receptor gene in men with impaired responsiveness to androgens in order to identify the molecular basis of their under-virilization. DESIGN: blood samples were used as the source of genomic dna. Portions of the androgen receptor gene were amplified by polymerase chain reaction and sequenced. patients: Samples were obtained from three patients and five normal fertile controls. patients were all 46 XY and were undervirilized with ambiguous external genitalia, gynaecomastia and infertility. MEASUREMENTS: Total cellular dna was purified from peripheral blood leucocytes. Pairs of oligonucleotide primers designed to flank the individual exons of the androgen receptor gene were synthesized. The specific regions of the androgen receptor were amplified from the samples of cellular dna by polymerase chain reaction. Amplified dna was purified, sequenced and compared to the published sequence. RESULTS: In all three patients point mutations in the androgen receptor gene were detected but no defects were detected in samples from normal controls. In two of the patients, an identical single nucleotide change from G to T was detected. This nucleotide was within the codon for amino acid 866 and would change it from valine to leucine. Amino acid 866 is found within an area of the steroid binding domain thought to be involved in receptor dimerization. Within the repetitive sequence of exon I patient 1 had 21 glutamine residues and patient 2 had 25. In the third patient a single change of G to A would result in incorporation of lysine in place of a conserved arginine residue at position 607 within the second zinc finger of the dna binding domain. The sequence of the androgen receptor gene of the mother of the third patient revealed her to be heterozygous for the same defect. CONCLUSION: patients 1 and 2 are unrelated although they have an identical point mutation in their androgen receptor gene. A patient with complete androgen insensitivity syndrome has been reported to have a defect at the same position causing the amino acid substitution of methionine for valine. Therefore we confirm that the nature of the amino acid change in the peptide sequence of the androgen receptor as well as its location within the protein, can have a profound effect on the phenotypic severity of androgen resistance. Studies on mutated receptors from individuals with a wide range of degrees of androgen resistance may enable us to construct a map of the key amino acids in the different domains of the protein.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
2/5. A testicular tumor resembling the sex cord with annular tubules in a case of the androgen insensitivity syndrome.sex cord tumor with annular tubules (SCTAT) is a distinctive neoplasm with indifferent cells of sex cord derivation in a characteristic arrangement of ring-like tubules. Much attention has been drawn to its association with the peutz-jeghers syndrome (PJS) with reported occurrence of the tumor in the testis of a boy with PJS. The authors present two cases of the androgen insensitivity syndrome (AIS), one of the cases being distinctive in having a large multicystic tumor resembling the SCTAT in the immature gonad. Additionally, the focal areas of the tumor, the large sertoli cells lining the tubules, resembled those of a large cell calcifying sertoli cell tumor (LCCSCT) although no calcific areas were discernible. Although the occurrence of neoplasms like germinomas and tubular adenomas is well known in the AIS, SCTAT has hitherto not been reported in a gonad of the AIS. SCTAT has been placed under an "unclassified sex cord-stromal" category in the world health organization (WHO) classification, yet, opinions are divided as to its origin from a granulosa or Sertoli cell, although an overlap in the histologic features of the two cell categories is to be anticipated in view of their homologous nature. In the case presented, the close resemblance of the tumor cells to the sertoli cells of the uninvolved gonad would further support the concept of a Sertoli line of differentiation of the SCTAT.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
3/5. Testicular feminisation syndrome: unusual gonadal histology in an elderly patient.The gonads of an elderly patient with a typical testicular feminisation syndrome are described. The unusual histological features consisted of total absence of testicular tubular structures or remnants thereof and distinct proliferation of smooth muscle bundles. In addition, there was fibrous proliferation, areas of ovarian stroma, and rare Reinke crystalloids within leydig cells. The complete tubular absence may have been the result of fibrous replacement related to patient's advanced age, while the muscular proliferation may have been of hamartomatous nature. Thus, it seems that in elderly patients with testicular feminisation syndrome, the histological appearance of the gonads may vary considerably from that in younger individuals, and in such cases the correct diagnosis should be based mainly on clinical and cytogenetic findings.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
4/5. peutz-jeghers syndrome with feminizing sertoli cell tumor.A case involving a 6-year-old boy with peutz-jeghers syndrome and an unilateral feminizing sertoli cell tumor is described. Endocrinologic studies revealed consistently high plasma and urine levels of estrogens and normal levels of testosterone and dihydrotestosterone. The increased levels of estrogens did not show changes that could be correlated with exogenous gonadotropin administration, thus indicating an autonomous nature. The histopathologic studies of nontumorous testicular tissue revealed changes in the seminiferous tubules which suggested that estrogens, directly or indirectly, may have had both stimulating and atrophying effects. It is concluded that gonadal tumors are in additional manifestation of the peutz-jeghers syndrome gene in both male and female patients.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
5/5. Corpus albicans-like structures in the gonads in androgen insensitivity syndrome.The complete androgen insensitivity syndrome is the most common form of male pseudohermaphroditism and is due to end-organ unresponsiveness to androgens. The patients are phenotypically female, but the genotype is 46, XY, and the gonads are testicles. However, the common presence of Sertoli cell adenomalike nodules of immature seminiferous tubules and the frequent presence of stroma resembling ovarian stroma may cause confusion about the nature of the gonad. Herein, we report the occurrence in such a gonad of corpus albicans-like structures, which resulted from progressive hyalinization and aggregation of immature tubules. These structures, which to our knowledge have not been previously described, must be recognized for what they represent to avoid misinterpretation in the pathologic evaluation of this disorder.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |