96:. Frasier syndrome in some infants may therefore go unrecognized until the affected child presents with signs of renal impairment and further testing is undertaken to evaluate the cause. In infants with XY genotype it causes an intersex condition as a result of gonadal dysgenesis. Although males with Frasier syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia may not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear completely female. The internal reproductive organs (gonads) are typically undeveloped and referred to as streak gonads.
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Both males and females can have
Frasier syndrome but their presentations can be different. Affected females usually have normal genitalia and gonads and have only the features of impaired renal function, which may not present until early childhood or even adolescence. Because females do not have all
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zinc fingers. Referring to the autosomal dominant expressive nature of this disease, it is only necessary for an individual to have one complement of the mutated intronic sequence to appear affected. Differing from the similar Denys-Drash syndrome, where a mutated form of the WT1 protein exists,
470:
Hastie, Nicholas D. (Aug 1992). "Dominant negative mutations in the Wilms tumour (WT1) gene cause Denys–Drash syndrome—proof that a tumour-suppressor gene plays a crucial role in normal genitourinary development".
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These abnormal gonads are nonfunctional and often become cancerous, so they are usually removed surgically early in life. Renal features of the condition include progressive glomerulonephropathy (focal segmental
203:, a specific ratio of the two isoforms normally exists, though the mutation in the intron 9 splice site severely lowers levels of the +KTS isoform; this leads to Frasier syndrome.
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and steroid resistant nephrotic syndrome can diagnose
Fraiser syndrome early, although the slow progression of renal failure makes diagnosis difficult.
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Ezaki, Jiro; Hashimoto, Kazunori; Asano, Tatsuo; Kanda, Shoichiro; Akioka, Yuko; Hattori, Motoshi; Yamamoto, Tomoko; Shibata, Noriyuki (2015-04-01).
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was highlighted in past studies looking at the related Denys–Drash syndrome. Results of various investigations identified the loss of function of
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Dai YL.; Fu JF.; Hong F.; et al. (Jul 2011). "WT1 mutation as a cause of 46 XY DSD and Wilm's tumour: a case report and literature review".
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153:. Its role as a transcription factor is related to proper kidney and gonadal development. The link between kidney and gonadal development and
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Frasier, SD; Bashore, SD; Bashore, RA; Mosier, HD (May 1964). "Gonadoblastoma associated with pure gonadal dysgenesis in monozygous twins".
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Barbaux S.; Niaudet P.; Gubler MC.; et al. (Dec 1997). "Donor splice-site mutations in WT1 are responsible for
Frasier syndrome".
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fashion, indicating the need for only one mutated allele in a cell to lead to expression of the disease. Mutations predominantly occur
221:, allowing for expression in an individual that has no family history of it. The mutations occur during gamete formation or early in
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the features of the condition (e.g. gonadal dysgenesis), females are usually given the diagnosis of isolated nephrotic syndrome
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267:"Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/−KTS splice isoforms"
199:: normal WT1 proteins including the KTS site (+KTS), and mutated, shortened proteins lacking the KTS site (−KTS). Through
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to be a prerequisite of Wilms' tumour development, and also a key trait of individuals with genital abnormalities.
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Frasier syndrome expression works solely on the existence of a changed ratio of KTS
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180:. Mutations in this region proved for the absence of three amino acids—
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Mutations responsible for
Frasier syndrome predominantly occur in
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583:"Gonadal Tumor in Frasier Syndrome: A Review and Classification"
128:. Differentiating between the two syndromes can be challenging.
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is different; whilst Denys–Drash syndrome is associated with
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Klamt B, Koziell A, Poulat F, et al. (April 1998).
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Reconstructive surgery is an option for this condition
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For the anatomical abnormality observed in 1965, see
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390:OMIM Entry – # 136680 – FRASIER SYNDROME
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124:, Frasier syndrome is associated with
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211:Frasier syndrome is inherited in an
83:It was first characterized in 1964.
562:. U.S. National Library of Medicine
451:. U.S. National Library of Medicine
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146:(at 11p13), and codes for a four
415:10.1111/j.1651-2227.2011.02167.x
599:10.1158/1940-6207.CAPR-14-0415
190:—between the third and fourth
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711:Genitourinary system diseases
369:10.1016/S0022-3476(64)80622-3
74:anomaly associated with the
80:(Wilms tumor 1 gene) gene.
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587:Cancer Prevention Research
306:Reference, Genetics Home.
44:obstetrics and gynaecology
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336:rarediseases.info.nih.gov
174:nucleotide substitutions
560:Genetics Home Reference
449:Genetics Home Reference
312:Genetics Home Reference
716:Male genital disorders
116:, and the tumour risk
201:alternative splicing
151:transcription factor
114:Denys-Drash syndrome
485:10.1093/hmg/1.5.293
284:10.1093/hmg/7.4.709
207:Inheritance pattern
172:gene, specifically
556:"Frasier syndrome"
523:10.1038/ng1297-467
308:"Frasier syndrome"
213:autosomal dominant
178:intron splice site
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148:zinc finger
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705:Categories
684:DiseasesDB
628:2022-01-01
357:J. Pediatr
341:2018-04-17
317:2018-04-17
249:References
235:amenorrhea
72:urogenital
721:Syndromes
607:1940-6207
241:Treatment
229:Diagnosis
168:9 of the
118:phenotype
35:Specialty
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539:10423058
431:39580813
423:21314844
377:14149008
197:isoforms
132:Genetics
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293:9499425
218:de novo
48:urology
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166:intron
98:Source
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619:S2CID
535:S2CID
445:"WT1"
427:S2CID
70:is a
673:MeSH
662:OMIM
611:PMID
603:ISSN
568:2014
527:PMID
489:PMID
457:2014
419:PMID
373:PMID
289:PMID
136:The
595:doi
519:doi
481:doi
411:doi
407:100
365:doi
279:doi
192:WT1
170:WT1
159:WT1
155:WT1
139:WT1
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77:WT1
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