1/7. A girl with bilateral ovarian tumours: frasier syndrome.frasier syndrome (FS) is characterised by male pseudohermaphroditism, slowly progressing nephropathy and frequent development of gonadoblastoma. The Wilms' tumour suppressor gene (WT1 gene) plays an important role in the development of the urogenital system and the gonads. A splice mutation in intron 9 of the WT1 gene was recently described in patients with FS. We analysed the WT1 gene of a Japanese patient with male pseudohermaphroditism, steroid resistant-nephr-opathy and gonadoblastoma by the polymerase chain reaction and direct sequencing and detected a heterozygous point mutation in intron 9. CONCLUSION: analysis of the Wilms' tumour suppressor gene in a patient with frasier syndrome by the polymerase chain reaction and direct sequencing detected a 5G -->A transition at a position of the second alternative splice region of exon 9, important for predicting the risk of the occurrence of Wilms' tumour.- - - - - - - - - - ranking = 1keywords = gonadoblastoma (Clic here for more details about this article) |
2/7. 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 = 1.5keywords = gonadoblastoma (Clic here for more details about this article) |
3/7. 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 = 2.5keywords = gonadoblastoma (Clic here for more details about this article) |
4/7. 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 = 0.5keywords = gonadoblastoma (Clic here for more details about this article) |
5/7. 46,XY phenotypic male with focal segmental glomerulosclerosis caused by the WT1 splice site mutation.OBJECTIVE: frasier syndrome is characterized by progressive glomerulopathy due to nonspecific focal and segmental glomerulosclerosis (FSGS), 46,XY sex reversal and the development of gonadoblastoma from dysgenetic gonads. Donor splice site heterozygous mutations in intron 9 of the Wilms' tumor gene (WT1) cause this disease. We investigated whether WT1 mutations showed clinical heterogeneity. patients AND methods: A 6-year-old phenotypic boy was diagnosed as having FSGS. His karyotype was 46,XY. gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests revealed normal luteinizing hormone, follicle-stimulating hormone and testosterone responses. The other patient was a 7-year-old 46,XY female with FSGS. Prophylactic gonadectomy was performed and gonadoblastoma was found. By polymerase chain reaction and direct sequencing, WT1 was analyzed in these patients. RESULTS AND CONCLUSION: Both patients had IVS9 5G-->A in intron 9 of the WT1. Our study indicates a normal 46,XY phenotypic male patient with FSGS. The phenotypic variations of the WT1 splice site mutations are further expanded.- - - - - - - - - - ranking = 1keywords = gonadoblastoma (Clic here for more details about this article) |
6/7. Slow progressive FSGS associated with an F392L WT1 mutation.Constitutional missense mutations in the WT1 gene are usually associated with the denys-drash syndrome, characterized by a rapid progressive nephropathy, male pseudohermaphroditism, and an increased risk for wilms tumor. We report here a patient with scrotal hypospadias and a slow progressive nephropathy due to focal and segmental glomerulosclerosis. WT1 mutation analysis revealed a constitutional missense mutation in exon 9 resulting in an exchange F392L. This mutation has previously been reported by others in a patient with a similar mild course of nephropathy. In contrast, a mutation in the corresponding codon of exon 8 (F364L) was previously found by us in a patient with a very rapid progression to end-stage renal disease. Whether the position of a mutation may influence the course of the nephropathy must be evaluated in a larger patient cohort. The individual tumor risk for this alteration cannot be given at present because neither of the two patients has shown evidence of a wilms tumor or a gonadoblastoma to date.- - - - - - - - - - ranking = 0.5keywords = gonadoblastoma (Clic here for more details about this article) |
7/7. 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 = 0.5keywords = gonadoblastoma (Clic here for more details about this article) |