1/4. An unusual phenotype of frasier syndrome due to IVS9 4C>T mutation in the WT1 gene: predominantly male ambiguous genitalia and absence of gonadal dysgenesis.The Wilms' tumor gene (WT1) encodes a zinc-finger transcription factor involved in the development of the kidneys and gonads and their subsequent normal function. Mutations in the WT1 gene were identified in patients with WAGR (Wilms' tumor, aniridria, genitourinary abnormalities, and mental retardation), denys-drash syndrome, and frasier syndrome (FS). Constitutional heterozygous mutations of the WT1 gene, almost all located at intron 9, are found in patients with FS. This syndrome is characterized by female external genitalia in 46,XY patients, late renal failure, streak gonads, and high risk of gonadoblastoma development. We report a male with FS with an unusual phenotype characterized by normal penis size with perineal hypospadias, end-stage renal failure at the age of 19 yr, normal adult male serum T levels, extremely elevated gonadotropin levels, para-testicular leiomyoma, unilateral testicular germ cell tumor, bilateral gonadoblastoma, and absence of gonadal dysgenesis. Automatic sequencing identified the IVS9 4C>T mutation in the WT1 gene, which predicts a change in splice site utilization. WT1 transcript analysis showed reversal of the normal positive/negative KTS (lysine, threonine, and serine) isoform ratio, confirming the diagnosis of FS. This patient with FS presents an external genitalia of denys-drash syndrome, suggesting that these two syndromes are not distinct diseases but may represent two ends of a spectrum of disorders caused by alterations in WT1 gene. This case expands the spectrum of phenotypes associated with WT1 mutations, by including predominantly male ambiguous genitalia and absence of gonadal dysgenesis, extremely high gonadotropin levels, and delayed adrenarche, and presence of a para-testicular leiomyoma, bilateral gonadoblastoma, and germ cell neoplasia.- - - - - - - - - - ranking = 1keywords = gonadal dysgenesis, dysgenesis (Clic here for more details about this article) |
2/4. gonadoblastoma and dysgerminoma associated with XY gonadal dysgenesis in an adolescent with chronic renal failure: a case of frasier syndrome.STUDY OBJECTIVES: To report a rare reason for primary amenorrhea, a frasier syndrome, XY gonadal dysgenesis associated with renal failure with eventual development of gonadoblastoma. To study immunohistochemical analysis of gonadoblastoma and dysgerminoma. To analyze the possibility of androgen receptor mutation in this rare syndrome. methods: We report a case of a 16-yr-old female with this syndrome. She underwent a laparoscopic bilateral gonadectomy and salpingectomy. A histopathological examination revealed gonadoblastoma with focal malignant dysgerminoma in the left dysgenetic gonad and an immunohistochemical of these fairly rare, malignant tumors. An androgen receptor was coded. Analysis was done. RESULTS: Immunohistochemical analysis showed that inhibin was strongly positive in gonadoblastoma but negative in dysgerminoma. No mutations of the androgen receptor gene were found. CONCLUSIONS: Inhibin positivity in gonadal stroma and in gonadoblastoma may indicate hormonal activity causing advanced puberty in patients with XY gonadal dysgenesis.- - - - - - - - - - ranking = 1keywords = gonadal dysgenesis, dysgenesis (Clic here for more details about this article) |
3/4. Molecular analysis of frasier syndrome: mutation in the WT1 gene in a girl with gonadal dysgenesis and nephronophthisis.The Wilms' tumor gene (WT1) encodes a protein that is believed to exert transcriptional and tumor-suppressor activities. Mutations in this gene have occasionally been associated with Wilms' tumor (<15% patients) and, more consistently, with three syndromes characterized by urogenital abnormalities (WAGR, Denys-Drash and Frasier syndromes). We report 17 years follow-up of a 29 year-old phenotypic female with 46,XY karyotype, gonadal dysgenesis and nephronophthisis in order to identify possible germline alterations of the WT1 gene. frasier syndrome was suspected and confirmed by genetic analysis. Sequence analysis permitted the identification of an A40-->G mutation in position 5 in the donor splice site of intron 9. During surgery for streak gonads extirpation, a microscopic gonadoblastoma was found, a typical complication of frasier syndrome.- - - - - - - - - - ranking = 0.83333333333333keywords = gonadal dysgenesis, dysgenesis (Clic here for more details about this article) |
4/4. frasier syndrome comes full circle: genetic studies performed in an original patient.frasier syndrome is a relatively rare disorder associated with XY gonadal dysgenesis, gonadoblastoma, and kidney failure. In this report, we identify a classic mutation in the Wilms' tumor 1 gene in one of the original cases of frasier syndrome reported in this Journal in 1964.- - - - - - - - - - ranking = 0.16666666666667keywords = gonadal dysgenesis, dysgenesis (Clic here for more details about this article) |