frasier syndrome


Summary: A syndrome characterized by CHRONIC KIDNEY FAILURE and GONADAL DYSGENESIS in phenotypic females with karyotype of 46,XY or female individual with a normal 46,XX karyotype. It is caused by donor splice-site mutations of Wilms tumor suppressor gene (GENES, WILMS TUMOR) on chromosome 11.

Top Publications

  1. Schumacher V, Gueler B, Looijenga L, Becker J, Amann K, Engers R, et al. Characteristics of testicular dysgenesis syndrome and decreased expression of SRY and SOX9 in Frasier syndrome. Mol Reprod Dev. 2008;75:1484-94 pubmed publisher
    b>Frasier syndrome (FS) is characterized by chronic renal failure in early adulthood, varying degrees of gonadal dysgenesis, and a high risk for gonadal germ cell malignancies, particularly gonadoblastoma...
  2. Hersmus R, van der Zwan Y, Stoop H, Bernard P, Sreenivasan R, Oosterhuis J, et al. A 46,XY female DSD patient with bilateral gonadoblastoma, a novel SRY missense mutation combined with a WT1 KTS splice-site mutation. PLoS ONE. 2012;7:e40858 pubmed publisher
    ..b>Frasier syndrome (FS) is characterized by gonadal dysgenesis with a high risk for development of GB as well as chronic renal ..
  3. Hashimoto K, Horibe Y, Ezaki J, Kanno T, Takahashi N, Akizawa Y, et al. Laparoscopically Removed Streak Gonad Revealed Gonadoblastoma in Frasier Syndrome. Anticancer Res. 2017;37:3975-3979 pubmed
    b>Frasier syndrome (FS) is characterized by gonadal dysgenesis and progressive nephropathy caused by mutation in the Wilm's tumor gene (WT1)...
  4. Yang Y, Feng D, Huang J, Nie X, Yu Z. A child with isolated nephrotic syndrome and WT1 mutation presenting as a 46, XY phenotypic male. Eur J Pediatr. 2013;172:127-9 pubmed publisher
    Mutations in the WT1 gene can lead to Denys-Drash syndrome or Frasier syndrome and can also cause isolated nephrotic syndrome (NS). Most patients with isolated NS caused by WT1 mutations present as 46, XX phenotypic females...
  5. Piekiełko Witkowska A, Nauman A. Alternative splicing and its role in pathologies of the endocrine system. Endokrynol Pol. 2011;62:160-70 pubmed
    ..cancers of the thyroid, prostate, ovary and breast, and insulinoma), isolated growth hormone deficiency, and Frasier syndrome. Non-endocrine pathologies in which aberrant alternative splicing of transcripts of genes involved in ..
  6. Saxena A, van Tuil C, Schultze Everding A. Frasier syndrome in a pre-menarchal girl: laparoscopic resection of gonadoblastoma. Eur J Pediatr. 2006;165:917-9 pubmed
    b>Frasier syndrome (FS) is characterized by male pseudohermaphroditism, slowly progressing nephropathy, and frequent development of gonadoblastoma. These patients are, however, often diagnosed when evaluated for primary amenorrhea...
  7. Orloff M, Iyengar S, Winkler C, Goddard K, Dart R, Ahuja T, et al. Variants in the Wilms' tumor gene are associated with focal segmental glomerulosclerosis in the African American population. Physiol Genomics. 2005;21:212-21 pubmed
    ..Furthermore, HIV-1 infection status interacts with genetic variations in both genes to influence this phenotype. We speculate that nephropathy liability alleles in WT1 pathway genes cause podocyte dysfunction and glomerular scarring. ..
  8. Stefanidis C, Querfeld U. The podocyte as a target: cyclosporin A in the management of the nephrotic syndrome caused by WT1 mutations. Eur J Pediatr. 2011;170:1377-83 pubmed publisher
    ..We review recent data on the role of WT1 in the development of WT1-GP and discuss putative therapeutic targets explaining the therapeutic effect of CsA. ..
  9. Carney T, Feitosa N, Sonntag C, Slanchev K, Kluger J, Kiyozumi D, et al. Genetic analysis of fin development in zebrafish identifies furin and hemicentin1 as potential novel fraser syndrome disease genes. PLoS Genet. 2010;6:e1000907 pubmed publisher
    ..In addition, the novel genes might prove helpful to unravel the molecular nature of thus far unresolved cases of the human disease. ..

More Information


  1. Mestrallet G, Bertholet Thomas A, Ranchin B, Bouvier R, Frappaz D, Cochat P. Recurrence of a dysgerminoma in Frasier syndrome. Pediatr Transplant. 2011;15:e53-5 pubmed publisher
    ..We report on a patient followed for FS revealed by acute peritoneal syndrome because of ovarian dysgerminoma. Therapeutic options had led to an unusual course with recurrent neoplastic disease after renal transplantation. ..
  2. Kanemoto K, Ishikura K, Ariyasu D, Hamasaki Y, Hataya H, Hasegawa Y, et al. WT1 intron 9 splice acceptor site mutation in a 46,XY male with focal segmental glomerulosclerosis. Pediatr Nephrol. 2007;22:454-8 pubmed
    ..Germline mutations of WT1 have been reported in patients with Denys-Drash syndrome (DDS) and Frasier syndrome (FS)...
  3. Aucella F, Bisceglia L, De Bonis P, Gigante M, Caridi G, Barbano G, et al. WT1 mutations in nephrotic syndrome revisited. High prevalence in young girls, associations and renal phenotypes. Pediatr Nephrol. 2006;21:1393-8 pubmed
    ..steroid resistance under 18 years presented classical WT1 splice mutations (IVS9+5G>A, IVS9+4C>T) of Frasier syndrome. Another one presented a mutation coding for an amino acid change (D396N) at exon 9 that is typical of Denys-..
  4. Zugor V, Zenker M, Schrott K, Schott G. [Frasier syndrome: a rare syndrome with WT1 gene mutation in pediatric urology]. Aktuelle Urol. 2006;37:64-6 pubmed
    ..To date, in many patients with Frasier syndrome WT1 mutations have been found, occurring exclusively as germ-line mutations of the alternative splicing donor ..
  5. Subbiah V, Huff V, Wolff J, Ketonen L, Lang F, Stewart J, et al. Bilateral gonadoblastoma with dysgerminoma and pilocytic astrocytoma with WT1 GT-IVS9 mutation: A 46 XY phenotypic female with Frasier syndrome. Pediatr Blood Cancer. 2009;53:1349-51 pubmed publisher
    b>Frasier syndrome is characterized by a 46 XY disorder of sex development, nephropathy, and increased risk for gonadoblastoma due to Wilms tumor 1(WT1) mutation in the donor splice site of intron-9, resulting in the splice form +KTS...
  6. Al Mulhim A, Kamal H. Ambiguous genitalia in neonates: a 4-year prospective study in a localized area. East Mediterr Health J. 2010;16:214-7 pubmed
    ..The karyotype was undetermined in 6 natients. Positive family history of ambiguous genitalia was noted in 4 patients...
  7. Sinha A, Sharma S, Gulati A, Sharma A, Agarwala S, Hari P, et al. Frasier syndrome: early gonadoblastoma and cyclosporine responsiveness. Pediatr Nephrol. 2010;25:2171-4 pubmed publisher
    b>Frasier syndrome is characterized by progressive glomerulopathy that is unresponsive to corticosteroids, male pseudohermaphroditism, and an increased risk of genitourinary tumors...
  8. Bache M, Dheu C, Doray B, Fothergill H, Soskin S, Paris F, et al. Frasier syndrome, a potential cause of end-stage renal failure in childhood. Pediatr Nephrol. 2010;25:549-52 pubmed publisher
    The diagnosis of Frasier syndrome is based on the association of male pseudohermaphroditism (as a result of gonadal dysgenesis), with steroid-resistant nephrotic syndrome due to focal and segmental glomerular sclerosis (FSGS), which ..
  9. Kitsiou Tzeli S, Deligiorgi M, Malaktari Skarantavou S, Vlachopoulos C, Megremis S, Fylaktou I, et al. Sertoli cell tumor and gonadoblastoma in an untreated 29-year-old 46,XY phenotypic male with Frasier syndrome carrying a WT1 IVS9+4C>T mutation. Hormones (Athens). 2012;11:361-7 pubmed
    b>Frasier syndrome (FS) phenotype in 46,XY patients usually consists of female external genitalia, gonadal dysgenesis, high risk of gonadoblastoma and the development of end stage renal failure usually in the second decade of life...
  10. Niaudet P, Gubler M. WT1 and glomerular diseases. Pediatr Nephrol. 2006;21:1653-60 pubmed
    ..Patients with Frasier syndrome present with normal female external genitalia, streak gonads, XY karyotype and progressive nephropathy with ..
  11. Andrade J, Guaragna M, Soardi F, Guerra Junior G, Mello M, Maciel Guerra A. Clinical and genetic findings of five patients with WT1-related disorders. Arq Bras Endocrinol Metabol. 2008;52:1236-43 pubmed
    ..The heterozygous IVS9+4, C>T mutation, compatible with Frasier syndrome was detected...
  12. Ismaili K, Pawtowski A, Boyer O, Wissing K, Janssen F, Hall M. Genetic forms of nephrotic syndrome: a single-center experience in Brussels. Pediatr Nephrol. 2009;24:287-94 pubmed publisher
    ..Genetic forms of nephrotic syndrome comprise a heterogeneous group of genetic mutations. The progression toward end-stage renal failure is the rule but is highly variable between patients...
  13. Merhi Z, Pollack S. Pituitary origin of persistently elevated human chorionic gonadotropin in a patient with gonadal failure. Fertil Steril. 2013;99:293-6 pubmed publisher
    ..Her past medical history was significant for focal segmental glomerulosclerosis, leading to a diagnosis of Frasier syndrome. At age 31 years, she desired pregnancy by oocyte donation and was found to have persistently elevated low ..
  14. Guaragna M, Lutaif A, Bittencourt V, Piveta C, Soardi F, Castro L, et al. Frasier syndrome: four new cases with unusual presentations. Arq Bras Endocrinol Metabol. 2012;56:525-32 pubmed
    b>Frasier syndrome (FS) is characterized by gonadal dysgenesis and nephropathy. It is caused by specific mutations in the Wilms' tumor suppressor gene (WT1) located in 11p23...
  15. Fujita S, Sugimoto K, Miyazawa T, Yanagida H, Tabata N, Okada M, et al. A female infant with Frasier syndrome showing splice site mutation in Wilms' tumor gene (WT1) intron 9. Clin Nephrol. 2010;73:487-91 pubmed
    ..The patient was then diagnosed with Frasier Syndrome (FS) on the basis of donor site mutation (IVS9+5G > A) of the splice site in the intron 9...
  16. Zwolinska D. [The genetic background of congenital nephrotic syndrome]. Przegl Lek. 2006;63 Suppl 3:10-1 pubmed
  17. Miyoshi Y, Santo Y, Tachikawa K, Namba N, Hirai H, Mushiake S, et al. Lack of puberty despite elevated estradiol in a 46,XY phenotypic female with Frasier syndrome. Endocr J. 2006;53:371-6 pubmed
    b>Frasier syndrome is characterized by slowly progressive nephropathy, male pseudohermaphroditism, streak gonad, and high risk of gonadoblastoma development...
  18. Matuszczak E, Debek W, Chomczyk I. Frasier syndrome in 17-year-old girl--case report. Ginekol Pol. 2011;82:468-70 pubmed
    The authors present a case of Frasier syndrome in a 17-year-old girl with nephrotic syndrome and male pseudohermaphroditism...
  19. Maruniak Chudek I, Niemir Z, Swietlinski J. [The genetic basis of childhood nephrotic syndrome]. Postepy Hig Med Dosw (Online). 2004;58:405-15 pubmed
    ..g. Finnish-type nephrotic, Denys-Drash and Frasier's syndromes, as well as sporadic focal-segmental glomerulosclerosis. A change in the routine policy used in evaluating the causes of childhood nephrotic syndrome is discussed. ..
  20. Chernin G, Vega Warner V, Schoeb D, Heeringa S, Ovunc B, Saisawat P, et al. Genotype/phenotype correlation in nephrotic syndrome caused by WT1 mutations. Clin J Am Soc Nephrol. 2010;5:1655-62 pubmed publisher
    ..These patients had isolated NS if karyotype was 46,XX and Frasier syndrome if karyotype was 46,XY...
  21. Auber F, Jeanpierre C, Denamur E, Jaubert F, Schleiermacher G, Patte C, et al. Management of Wilms tumors in Drash and Frasier syndromes. Pediatr Blood Cancer. 2009;52:55-9 pubmed publisher
    Children with WT1 gene-related disorders such as Denys-Drash syndrome (DDS) and Frasier syndrome (FS) are at increased risk of Wilms tumor and end-stage renal disease...
  22. Morrison A, Viney R, Saleem M, Ladomery M. New insights into the function of the Wilms tumor suppressor gene WT1 in podocytes. Am J Physiol Renal Physiol. 2008;295:F12-7 pubmed publisher
    ..Recent advances including the development of transgenic mouse models and conditionally immortalized podocyte cell lines are beginning to shed light on WT1's crucial role in podocyte function. ..
  23. Kohsaka T, Tagawa M, Koinuma S, Yamada M. [Frasier syndrome]. Nihon Rinsho. 2006;Suppl 2:499-504 pubmed
  24. Chan W, To K, But W, Lee K. Frasier syndrome: a rare cause of delayed puberty. Hong Kong Med J. 2006;12:225-7 pubmed
    ..A diagnosis of Frasier syndrome was made and she underwent laparoscopic gonadectomy...
  25. Wasilewska A, Zoch Zwierz W, Tenderenda E, Rybi Szuminska A, Kołodziejczyk Z. [WT1 mutation as a cause of progressive nephropathy in Frasier syndrome--case report]. Pol Merkur Lekarski. 2009;26:642-4 pubmed
    b>Frasier syndrome is an uncommon genetic disorder featuring progressive glomerulopathy, male pseudohermaphroditism and gonadal dysgenesis. It is caused by mutations in intron 9 of the WT1 gene...
  26. Nso Roca A, Peña Carrión A, Benito Gutiérrez M, Garcia Meseguer C, Garcia Pose A, Navarro M. Evolutive study of children with diffuse mesangial sclerosis. Pediatr Nephrol. 2009;24:1013-9 pubmed publisher
    ..We studied 14 patients, four with incomplete Denys-Drash syndrome and one with Frasier syndrome. All patients developed renal failure...
  27. Gwin K, Cajaiba M, Caminoa Lizarralde A, Picazo M, Nistal M, Reyes Mugica M. Expanding the clinical spectrum of Frasier syndrome. Pediatr Dev Pathol. 2008;11:122-7 pubmed
    b>Frasier syndrome is an uncommon genetic disorder featuring progressive glomerulopathy, male pseudohermaphroditism, and gonadal dysgenesis with increased risk of gonadoblastoma and malignant germ cell tumors...
  28. Love J, DeMartini S, Coppola C. Prophylactic bilateral salpingo-oopherectomy in a 17-year-old with Frasier syndrome reveals gonadoblastoma and seminoma: a case report. J Pediatr Surg. 2006;41:e1-4 pubmed
    Mutations in the Wilms' tumor gene are present in children with Frasier syndrome, Denys-Drash syndrome, WAGR syndrome, and some cases of Wilms' tumor. The Wilms' tumor gene product, WT1, is necessary for normal urogenital development...