Frasier Syndrome

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.

Also Known As:

Networked: 30 relevant articles (1 outcomes, 0 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Gonadoblastoma
2.	Disorders of Sex Development (Intersexuality)
3.	Wilms Tumor (Wilm's Tumor)
4.	Neoplasms (Cancer)
5.	46,XY Disorder of Sex Development (Male Pseudohermaphroditism)

Experts

1.	To, K F: 2 articles (10/2017 - 06/2006)
2.	Schedl, Andreas: 2 articles (12/2016 - 09/2009)
3.	But, W M: 2 articles (12/2015 - 06/2006)
4.	Karipiadou, Aristea: 1 article (11/2022)
5.	Kollios, Konstantinos: 1 article (11/2022)
6.	Kosta, Konstantina: 1 article (11/2022)
7.	Papagianni, Maria: 1 article (11/2022)
8.	Roilides, Emmanuel: 1 article (11/2022)
9.	Savvidou, Parthena: 1 article (11/2022)
10.	Stabouli, Stella: 1 article (11/2022)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Frasier Syndrome:

1.	Cyclosporine (Ciclosporin)FDA LinkGeneric 01/01/2019 - "In conclusion, the long-lasting treatment of once-daily low-dose cyclosporine A with RAS inhibition was effective for induction and maintenance of partial remission in Frasier syndrome." 10/01/2010 - "Frasier syndrome: early gonadoblastoma and cyclosporine responsiveness." 01/01/2019 - "Once-Daily Low-Dose Cyclosporine A Treatment with Angiotensin Blockade for Long-Term Remission of Nephropathy in Frasier Syndrome."
2.	AngiotensinsIBA 01/01/2019 - "Once-Daily Low-Dose Cyclosporine A Treatment with Angiotensin Blockade for Long-Term Remission of Nephropathy in Frasier Syndrome."
3.	Protein Isoforms (Isoforms)IBA 01/01/2015 - "Intron 9 splice-site mutations that influence the balance between WT1 isoforms cause a nearly similar phenotype, known as Frasier syndrome. " 11/01/2006 - "Germline intronic mutations leading to the loss of the +KTS isoforms have been observed in all patients with Frasier syndrome. " 05/01/2000 - "Mutations within the +/-KTS splice junction lead to severe urogenital developmental abnormalities such as Frasier syndrome, indicating that the isoform ratio is critical for wild-type function. " 01/01/1999 - "We report new mutations in exon 9 of the WT1 gene that did not alter the ratio of +/- KTS splice isoforms in two unrelated patients with Frasier syndrome (FS). " 01/01/1999 - "Exon 9 mutations in the WT1 gene, without influencing KTS splice isoforms, are also responsible for Frasier syndrome."
4.	RNA Splice SitesIBA 01/01/2020 - "Identification of a de novo Wilms tumor 1 splice donor-site mutation in intron 9 (NM_024426.6:c.1447 + 4C > T) and 46,XY-gonadal dysgenesis led to the diagnosis of Frasier syndrome. " 03/17/2023 - "Frasier syndrome (FS) is a rare inherited disorder characterized by gonadal dysgenesis and progressive nephropathy, resulting from mutations in the intron 9 splice donor site of the Wilms tumor 1 (WT1) gene. " 04/01/2000 - "We report a case where genetic analysis showed a WT1 mutation typically associated with Frasier syndrome: a 1228 + 5 guanine to adenine substitution at the 3' alternative splice donor site in intron 9. The case provides a focus for the discussion of recent evidence that Denys Drash and Frasier syndrome form two ends of a spectrum of disorders. " 10/01/1999 - "The intron 9 alternative splice donor site mutation seen in Frasier syndrome leads to loss of three amino acids (+KTS isoform), thus disrupting the normal ratio of the +KTS/-KTS isoforms critical for proper gonadal and renal development. " 07/21/2021 - "Frasier syndrome is caused by mutations in the splice donor site at intron 9 of the Wilms' tumor WT1 gene; these mutations result in an imbalanced ratio of WT1 protein isoforms and affect the development of the urogenital tract, podocyte function, and tumor suppression. "
5.	SteroidsIBA 10/01/2006 - "Three girls out of 32 of the group with steroid resistance under 18 years presented classical WT1 splice mutations (IVS9+5G>A, IVS9+4C>T) of Frasier syndrome. " 07/21/2021 - "Patients who have Frasier syndrome develop nephrotic syndrome (NS) featuring focal segmental glomerulosclerosis (FSGS) that is resistant to steroid treatment in early childhood. " 02/01/2002 - "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. 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."
6.	GuanineIBA 01/01/2001 - "In fact, direct sequencing of the PCR product of the intron 9 donor splice site revealed a substitution of guanine for adenine in position +5. Besides being one of the few Frasier syndrome cases to be genetically characterized, this case is interesting because of the unusually early-onset renal failure." 04/01/2000 - "We report a case where genetic analysis showed a WT1 mutation typically associated with Frasier syndrome: a 1228 + 5 guanine to adenine substitution at the 3' alternative splice donor site in intron 9. The case provides a focus for the discussion of recent evidence that Denys Drash and Frasier syndrome form two ends of a spectrum of disorders. "
7.	Antigen-Antibody Complex (Immune Complex)IBA 10/01/2022 - "These case reports support expansion of the clinical spectrum of the kidney phenotypes associated with Frasier syndrome providing evidence of an association between WT1 mutation and an immune complex-related membranoproliferative glomerulonephritis. " 01/01/2020 - "Immune-complex glomerulonephritis with a membranoproliferative pattern in Frasier syndrome: a case report and review of the literature."
8.	AdenineFDA LinkGeneric 01/01/2001 - "In fact, direct sequencing of the PCR product of the intron 9 donor splice site revealed a substitution of guanine for adenine in position +5. Besides being one of the few Frasier syndrome cases to be genetically characterized, this case is interesting because of the unusually early-onset renal failure." 04/01/2000 - "We report a case where genetic analysis showed a WT1 mutation typically associated with Frasier syndrome: a 1228 + 5 guanine to adenine substitution at the 3' alternative splice donor site in intron 9. The case provides a focus for the discussion of recent evidence that Denys Drash and Frasier syndrome form two ends of a spectrum of disorders. "
9.	RNA IsoformsIBA 08/01/2008 - "Disruption of the characteristic +KTS to -KTS ratio of mRNA isoforms as a result of mutations in the +KTS splice site results in Frasier syndrome. "
10.	WT1 ProteinsIBA 07/21/2021 - "Frasier syndrome is caused by mutations in the splice donor site at intron 9 of the Wilms' tumor WT1 gene; these mutations result in an imbalanced ratio of WT1 protein isoforms and affect the development of the urogenital tract, podocyte function, and tumor suppression. "

Therapies and Procedures

1.	Castration 10/01/2010 - "Patients with Frasier syndrome might benefit from early gonadectomy." 06/01/2006 - "A diagnosis of Frasier syndrome was made and she underwent laparoscopic gonadectomy. " 01/01/2006 - "For children with Frasier syndrome confirmed by molecular genetic analysis and loss of function of the testicles, we recommend performance of a prophylactic castration. " 01/01/2003 - "One of these XY patients had female phenotype (Frasier syndrome); she was raised as a girl with bilateral gonadectomy. " 11/01/2022 - "Bilateral Gonadoblastoma in a 6-Year-old Girl With Frasier Syndrome: Need for Early Preventive Gonadectomy."
2.	Transplantation 01/01/2001 - "The patient had a history of post-streptococcal glomerulonephrosis, when aged 4 years, which had rapidly progressed to kidney failure, requiring transplantation at age 8. Frasier syndrome was suspected and confirmed by genetic analysis. "
3.	Renal Dialysis (Hemodialysis) 06/01/2006 - "Here we report a case of a 46,XY phenotypic female with Frasier syndrome, who was under hemodialysis. "