Mutational analysis of NPHS2 and WT1 in frequently relapsing and steroid-dependent nephrotic syndrome.
Journal Article (Journal Article)
Idiopathic nephrotic syndrome is a common pediatric kidney disease, 80% of all cases are steroid sensitive (SSNS). A significant proportion of children with SSNS will have a frequently relapsing or steroid-dependent course (FRNS/SDNS) that is associated with significant treatment-related morbidity. Mutations in NPHS2 account for more than 28% of all cases of steroid-resistant nephrotic syndrome (SRNS) and dominant mutations in WT1 for 5%; while mutations are absent from children with uncomplicated SSNS. Since FRNS/SDNS is phenotypically positioned within a spectrum between SSNS and SRNS, we hypothesized that heterozygous mutations of NPHS2 may be causing FRNS/SDNS. Mutational analysis of NPHS2 and WT1 was carried out in a single-center cohort of 20 children with FRNS/SDNS, ten children with uncomplicated SSNS (control), and 22 children with SRNS (control). Renal biopsy findings were available in 15/20 children with FRNS/SDNS and revealed IgM nephropathy, MCNS, and FSGS in six, five, and four children, respectively. Children with FRNS/SDNS were significantly younger at first presentation than those with SSNS and SRNS (median age: 3.0 years in FRNS/SDNS patients, 7.0 years in SSNS patients, and 5.0 in SRNS patients; p < 0.001). No NPHS2 or WT1 mutations were found in patients with FRNS/SDNS and uncomplicated SSNS. The hypothesis that FRNS/SDNS may be associated with heterozygous mutations in NPHS2 or WT1 was not confirmed.
Full Text
Duke Authors
Cited Authors
- Gbadegesin, R; Hinkes, B; Vlangos, C; Mucha, B; Liu, J; Hopcian, J; Hildebrandt, F
Published Date
- April 2007
Published In
Volume / Issue
- 22 / 4
Start / End Page
- 509 - 513
PubMed ID
- 17216259
International Standard Serial Number (ISSN)
- 0931-041X
Digital Object Identifier (DOI)
- 10.1007/s00467-006-0377-y
Language
- eng
Conference Location
- Germany