| WT1 mutations in nephrotic syndrome revisited. High prevalence in young girls, associations and renal phenotypes. | |
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MedLine Citation:
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PMID: 16909243 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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WT1 mutations have been considered a rare cause of nephrotic syndrome but recent reports challenge this assumption. Exclusion of inherited forms is a basic point in any therapeutic strategy to nephrotic syndrome since they do not respond to drugs. We screened for WT1 mutations in 200 patients with nephrotic syndrome: 114 with steroid resistance (SRNS) and 86 with steroid dependence (SDNS) for whom other inherited forms of nephrotic syndrome (NPHS2, CD2AP) had been previously excluded. 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. Another one presented a mutation coding for an amino acid change (D396N) at exon 9 that is typical of Denys-Drash syndrome. All presented resistance to drugs and developed end stage renal failure within 15 years. Two girls of the Frasier group presented a 46 XY karyotype with streak gonads while one was XX and had normal gonad morphology. In the two cases with IVS9+5G>A renal pathology was characterized by capillary wall thickening with deposition of IgG and C3 in one that was interpreted as a membrane pathology. Foam cells were diffuse in tubule-interstitial areas. In conclusion, WT1 splice mutations are not rare in females under 18 years with SRNS. This occurs in absence of a clear renal pathology picture and frequently in absence of phenotype change typical of Frasier syndrome. In adults and children with SDNS, screening analysis is of no clinical value. WT1 hot spot mutation analysis should be routinely done in children with SRNS; if the molecular screening anticipates any further therapeutic approach it may modify the long term therapeutic strategy. |
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Authors:
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Filippo Aucella; Luigi Bisceglia; Patrizia De Bonis; Maddalena Gigante; Gianluca Caridi; Giancarlo Barbano; Gerolamo Mattioli; Francesco Perfumo; Loreto Gesualdo; Gian Marco Ghiggeri |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-08-15 |
Journal Detail:
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Title: Pediatric nephrology (Berlin, Germany) Volume: 21 ISSN: 0931-041X ISO Abbreviation: Pediatr. Nephrol. Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-08-25 Completed Date: 2006-12-07 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8708728 Medline TA: Pediatr Nephrol Country: Germany |
Other Details:
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Languages: eng Pagination: 1393-8 Citation Subset: IM |
Affiliation:
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Nephrology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Age Factors Child Child, Preschool DNA Mutational Analysis Denys-Drash Syndrome / genetics, pathology Drug Resistance Exons / genetics Female Frasier Syndrome / genetics, pathology Genetic Testing Humans Karyotyping Kidney / pathology* Male Mutation / genetics* Nephrotic Syndrome / drug therapy, genetics*, pathology* Phenotype* Prevalence Sex Factors Steroids / pharmacology WT1 Proteins / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Steroids; 0/WT1 Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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