PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Frasier Syndrome”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2006

Lack of puberty despite elevated estradiol in a 46,XY phenotypic female with Frasier syndrome.

Frasier syndrome is characterized by slowly progressive nephropathy, male pseudohermaphroditism, streak gonad, and high risk of gonadoblastoma development. Here we report a case of a 46,XY phenotypic female with Frasier syndrome, who was under hemodialysis. While her serum estradiol level was gradually increasing annually, gonadotropin level was constantly extremely high, and her appearance was still prepubertal. She was heterozygous for a novel guanine>adenine point mutation at position +1 of the splice donor site within intron 9 (IVS 9 + 1G>A) of the Wilms' tumor 1 gene. The possibility of this disease should be taken into consideration whenever we encounter a patient with steroid-resistant nephrotic syndrome and delayed puberty.

Adolescent↗
PubMed2004

Twenty-eight-year-old female with primary amenorrhea and chronic renal failure: a case of Frasier syndrome?

Frasier syndrome is a very rare developmental disorder of autosomal recessive inheritance. It is characterized by male hermaphroditism, primary amenorrhea, chronic renal failure (CRF), and a number of other abnormalities. A 28-year-old Nigerian female who was considered as a possible case of Frasier syndrome first presented to us in July 2002 with primary amenorrhea, congenital bilateral absence of middle toes, elevated blood pressure, and the uremic syndrome. The management of the case was mainly conservative, including blood pressure control with appropriate antihypertensives. The problems inherent in this index case are discussed while proffering appropriate management approach in a near-ideal situation, which unfortunately is nonexistent in our local environment. The presentation of this case is informed by the need to create awareness about this rare syndrome being a possible cause of CRF in some of our patients.

Adult↗
PubMed1997

Donor splice-site mutations in WT1 are responsible for Frasier syndrome.

Frasier syndrome (FS) is a rare disease defined by male pseudo-hermaphroditism and progressive glomerulopathy. Patients present with normal female external genitalia, streak gonads and XY karyotype and frequently develop gonadoblastoma. Glomerular symptoms consist of childhood proteinuria and nephrotic syndrome, characterized by unspecific focal and segmental glomerular sclerosis, progressing to end-stage renal failure in adolescence or early adulthood. No case of Wilms' tumour has been reported, even in patients with extended follow-up. In contrast with FS patients, most individuals with Denys-Drash syndrome (DDS; refs 6,7) have ambiguous genitalia or a female phenotype, an XY karyotype and dysgenetic gonads. Renal symptoms are characterized by diffuse mesangial sclerosis, usually before the age of one year, and patients frequently develop Wilms' tumour. Mutations of the Wilms'-tumour gene, WT1, cause different pathologies of the urogenital system, including DDS. WT1 is composed of ten exons and encodes a protein with four zinc-finger motifs and transcriptional and tumour-suppressor activities. Alternative splicing generates four isoforms: the fifth exon may or may not be present, and an alternative splice site in intron 9 allows the addition of three amino acids (KTS) between the third and fourth zinc fingers of WT1 (ref. 17). Here we demonstrate that FS is caused by mutations in the donor splice site in intron 9 of WT1, with the predicted loss of the +KTS isoform. Examination of WT1 transcripts indeed showed a diminution of the +KTS/-KTS isoform ratio in patients with FS.

Adult↗
PubMed2002

A girl with bilateral ovarian tumours: Frasier syndrome.

UNLABELLED: 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.

Base Sequence↗
PubMed1992

Molecular analysis of the sex-determining region from the Y chromosome in two patients with Frasier syndrome.

In the Frasier syndrome there is an association between XY gonadal dysgenesis and chronic renal failure. Owing to an observed sex reversal, the Y chromosomes of two girls with this syndrome have been analyzed. Using molecular-biology techniques, no major alterations of the known sex-determining area of the Y chromosome were found. Furthermore, the sequence did not reveal impairment of the recently described testis-determining factor SRY. These data suggest that in the Frasier syndrome, XY sex reversal and renal failure could be the result of either faulty gene(s) located downstream in the sex differentiation pathway during embryogenesis, or impaired SRY regulation. Preliminary results on the Wilms' tumor suppressor gene WT1, a candidate for acting downstream to SRY, are also provided.

Adolescent↗
PubMed2002

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.

Adrenal Cortex↗
PubMed2003

Alport syndrome-like basement membrane changes in Frasier syndrome: an electron microscopy study.

Frasier syndrome (FS) is a rare disease characterized by male pseudohermaphroditism and slowly progressing nephropathy. FS originates from heterozygous mutation in the intron 9 splicing donor site of Wilms' tumor suppressor gene (WT1). Focal segmental glomerular sclerosis is common in FS, but there have not been so many detailed pathologic investigations. The authors examined the kidneys of 3 patients with FS. The results showed that nephropathy started as mesangial proliferative glomerulonephritis, and later a concomitant focal segmental lesion developed. In all cases, electron microscopy results showed widespread thinning, splitting, and lamellation of the glomerular basement membrane, which mimicked hereditary nephritis. Throughout adulthood, WT1 protein expresses on glomerular podocytes. Recent reports described that podocytes expressing WT1 play an important role in maintaining the glomerular basement membrane. Hereditary nephritis-like glomerular basement membrane findings in FS suggest that one of the important functions of podocytes is to form and maintain the glomerular basement membrane.

Basement Membrane↗
PubMed2006

[Frasier syndrome: a rare syndrome with WT1 gene mutation in pediatric urology].

INTRODUCTION: Frasier syndrom is an autosomal dominant, hereditary disease characterized by nephropathy, gonadal dysgenesis and risk of gonadal blastoma in early childhood. To date, in many patients with Frasier syndrome WT1 mutations have been found, occurring exclusively as germ-line mutations of the alternative splicing donor site in intron 9. A Wilms tumor is seen only rarely in this clinical entity. In the present paper we describe the clinical course of a patient with Frasier syndrome confirmed by molecular genetic analysis. CASE REPORT: Our patient with Frasier syndrome as confirmed by molecular genetic analysis is now 19 years old. The patient became dependent on dialysis due to nethropathy in the form of focal sclerosing glomerulonephritis and terminal renal insufficiency. A kidney transplantation in the left iliac fossa together with new implantation of the ureter according to Dodson. For prophylactic reasons on account of the high risk of gonadal blastoma associated with the disease and sonographically detected microlithiasis in both testicles we performed one year later an inguinal castration. Histology revealed the picture of a severe tubular testicular atrophy with arrested spermatogenesis and focal intratubular germ-line neoplasia. CONCLUSIONS: This case report shows that, besides our already published series with Denys-Drash syndrome, WT1 mutations may also be associated with the so-called Frasier syndrome. For children with Frasier syndrome confirmed by molecular genetic analysis and loss of function of the testicles, we recommend performance of a prophylactic castration. We also suggest that phenotypical female patients with focal sclerosing glomerulonephritis be examined for WT1 mutations.

Adolescent↗
PubMed1999

Frasier syndrome: a cause of focal segmental glomerulosclerosis in a 46,XX female.

The description of Frasier syndrome until now has been restricted to XY females with gonadal dysgenesis, progressive glomerulopathy, and a significant risk of gonadoblastoma. Mutations in the donor splice site in intron 9 of the Wilms' tumor (WT1) gene have been shown to cause Frasier syndrome and are distinct from WT1 exon mutations associated with Denys-Drash syndrome. The WT1 gene, which is essential for normal kidney and gonadal development, encodes a zinc finger transcription factor. 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. This study examines two sisters with identical intron 9 mutations. The proband carries a classic diagnosis of Frasier syndrome with 46,XY gonadal dysgenesis, whereas her sister has progressive glomerulopathy but a 46,XX karyotype and normal female development. This indicates that the proper WT1 isoform ratio is critical for renal and testicular development, but apparently does not affect either ovarian development or function. It is proposed that the clinical definition of Frasier syndrome should be broadened to include 46,XX females with normal genital development and focal segmental glomerulosclerosis associated with a WT1 intron 9 donor splice site mutation. Nephrologists need to consider the possibility of this heritable syndrome in evaluation of females with focal segmental glomerulosclerosis and to consider their risk for gonadal malignancy, as well as the risk for kidney disease, gonadal dysgenesis, and malignancy in their offspring.

Adolescent↗
PubMed2006

Prophylactic bilateral salpingo-oopherectomy in a 17-year-old with Frasier syndrome reveals gonadoblastoma and seminoma: a case report.

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. Frasier syndrome is an association between focal segmental glomerulosclerosis, beginning in the second and third decade, male to female sex reversal, and dysgenetic gonads. We report a case of Frasier syndrome in a 17-year-old adolescent girl with renal failure, kidney transplant, and dysgenetic gonads, with development of gonadoblastoma and dysgerminoma (seminoma). The diagnosis of Frasier syndrome was based on nephrotic syndrome with diffuse mesangial sclerosis leading to chronic renal failure, dysgenetic gonads, 46 XY karyotype in a phenotypic female, and a mutation in the Wilms' tumor gene. Prophylactic laparoscopic bilateral salpingo-oopherectomy revealed gonadoblastoma and seminoma in opposite atrophic ovaries as well as a hypoplastic uterus. Early prophylactic resection of dysgenetic gonads is indicated in children with Frasier syndrome to prevent the development of germ cell malignancy.

Adolescent↗
PubMed2001

Clinical spectrum of Denys-Drash and Frasier syndrome.

Denys-Drash syndrome (DDS) and Frasier syndrome (FS) are two related conditions caused by mutations of the Wilms tumor gene, WT1. Both syndromes are characterized by male pseudohermaphroditism, a progressive glomerulopathy, and the development of genitourinary tumors. DDS and FS have previously been distinguished by differences in nephropathy, with DDS patients demonstrating diffuse mesangial sclerosis (DMS) in contrast to focal and segmental glomerulosclerosis (FSGS) in FS patients. The clinicopathological features and genotype analysis of two patients with WT1 mutations are presented in this report. Genotype analysis of the first patient revealed a previously undescribed mutation in exon 8 of the WT1 gene. The second patient presented with a rapidly progressive nephropathy characterized histologically by DMS, but was found to have the genetic mutation seen in FS patients. A summary of all reported patients with the characteristic mutation associated with FS demonstrates the clinical overlap of this syndrome with DDS. This suggests that both these conditions should be considered as part of the spectrum of disease due to WT1 gene mutations rather than as separate diseases. Clinical classification remains important for prognosis, as the underlying renal disease appears to predict the progression of nephropathy independently of the genetic abnormality.

Base Sequence↗
PubMedDate not supplied

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.

Adult↗
PubMed2001

Frasier syndrome with childhood-onset renal failure.

BACKGROUND: The Wilms' tumour 1 (WT1) gene encodes a protein which is believed to exert transcriptional and tumour-suppressor activities. Mutations of this gene have occasionally been associated with Wilms' tumour (<15% of cases) and, more consistently, with three syndromes characterized by urogenital abnormalities (WAGR, Denys-Drash and Frasier syndrome). SUBJECT/METHOD: A 25-year-old phenotypic female with a 46,XY karyotype presented with amenorrhoea. An ultrasound scan showed streak gonads and a rudimentary uterus. 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. RESULT: Frasier syndrome was suspected and confirmed by genetic analysis. 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. CONCLUSION: 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.

Adult↗
PubMed2000

Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?

Dysfunction of the Wilms' Tumour gene (WT1), a transcription factor critical for normal development and function of the urogenital tract, can result in both tumourigenesis [corrected] and urogenital abnormalities. The association of WT1 gene mutations with most cases of Denys-Drash syndrome is well described. More recently WT1 mutations have also been described in a related condition, Frasier syndrome. 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. In addition, it illustrates the increasing significance of genetic investigation within clinical practice for diagnostic, prognostic and therapeutic purposes and the importance of karyotype analysis in phenotypically normal girls with renal disease.

Adolescent↗
PubMed2002

Gonadal mosaicism of Frasier syndrome in 3 Chinese siblings with donor splice site mutation of Wilms' tumour gene.

Frasier syndrome is a rare human developmental disorder classically affecting 46,XY females and leading to male pseudohermaphroditism and chronic renal failure. We describe a family with both 46,XX and 46,XY females affected by the syndrome due to WT1 splice site mutations. The diagnosis of Frasier syndrome in 1 of the children led to the discovery of the syndrome in 2 other siblings, of whom 1 is asymptomatic. Since the mutation was not found in either parents, gonadal mosaicism was suggested. The implication of family screening for WT1 gene mutation in asymptomatic members is also discussed.

Adolescent↗
PubMed1999

A Japanese case with Frasier syndrome caused by the splice junction mutation of WT1 gene.

The Wilms' tumor suppressor gene, WT1, plays an important role in the development of the urogenital system and also subsequent normal function of this system. Recently, the splice mutations in intron 9 of WT1 gene have been detected in Frasier syndrome, which is characterized by streak gonads, pseudohermaphroditism, slowly progressive nephropathy and frequent development of gonadoblastoma. Here to elucidate the molecular basis in a Japanese patient of Frasier syndrome, WT1 gene was analyzed by polymerase-chain-reaction (PCR) and direct sequencing. We identified the splice junction mutation in intron 9 of WT1, which is recognized as a mutation hot-spot in intron 9. This finding concludes that 1) the mutation in intron 9 might be the cause of Frasier syndrome, and 2) the mutation hot-spot in Japanese and Caucasian patients is similar.

Adolescent↗
PubMed2006

Frasier syndrome in a pre-menarchal girl: laparoscopic resection of gonadoblastoma.

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. We report the case of FS in a pre-menarchal girl at the age of 6 years. Ultrasound examinations were performed and were inconclusive as to the presence or size of the gonads. Diagnostic laparoscopy was performed and the presence of bilateral streak gonads was documented and a bilateral salpingo-oophorectomy was performed. The postoperative course was uneventful. Histological examination of the streak gonads confirmed the presence of gonadoblastoma. To our knowledge, this is the first case in the literature of a pre-menarchal patient diagnosed with FS and a laparoscopic bilateral gonadoblastoma resection. Laparoscopic aspects regarding safe streak gonad removal in the pediatric population have been elaborated.

Child↗