Membranoproliferative glomerulonephritis associated with a mutation in Wilms’ tumour suppressor gene 1

Böckenhauer, Detlef; Hoff, William van’t; Chernin, Gil; Heeringa, Saskia F.; Sebire, Neil J.

doi:10.1007/s00467-009-1135-8

Cited by 10 publications

(18 citation statements)

References 13 publications

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“…Mutations in the WT1 gene in patients with SRNS seem to be restricted to exons 8 and 9 [7]. WT1 mutations in patients with SRNS are associated with FSGS, diffuse mesangial sclerosis (DMS) or membranoproliferative glomerulonephritis [2] on biopsy. Interestingly, the same WT1 mutation (1228 +5 G>A) may be associated with different phenotypes and glomerular diseases in the same family, as shown by Denamur et al who found transmission of this mutation from a phenotypically normal (karyotype XX) mother with proteinuria and FSGS to a child with the Denys-Drash syndrome (karyotype XY) and DMS [18].…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in the WT1 gene result in the occurrence of diffuse mesangial sclerosis (DMS), focal segmental glomerulosclerosis (FSGS), or membranoproliferative glomerulonephritis [2], which may appear isolated or in combination with other features, such as in the Denys-Drash and Frasier syndromes [1]. WT1 mutations have been found in a small percentage of children with isolated or syndromal steroid-resistant nephrotic syndrome (SRNS) [3][4][5], but have not been described in patients with steroid-sensitive nephrotic syndrome (SSNS) [6].…”

Section: Introductionmentioning

confidence: 99%

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Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations

et al. 2010

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The Wilms' tumor suppressor gene 1 (WT1) encodes a transcription factor involved in kidney and gonadal development. WT1 is also a key regulator of podocyte functions and mutations have been found in a small percentage of children with isolated or syndromal steroid-resistant nephrotic syndrome. It is commonly assumed that the nephrotic syndrome (NS) in patients with WT1 mutations is unresponsive to therapy and characterized by rapid progression to end-stage renal disease. We report long-term observations in 3 children with focal-segmental glomerulosclerosis associated with WT1 mutations and NS (2 cases) or nephrotic range proteinuria (1 case). All patients showed a favorable response to an intensified therapy consisting of cyclosporin A (CyA) in combination with induction therapy with intravenous and oral prednisone. Treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was added to the regimen at various times. As shown both by the short-term response and during long-term follow-up, this treatment resulted in clinical remission of the NS and/or significant reduction of proteinuria, while normal renal function could be maintained over many years. Thus, glomerular diseases in selected patients with mutations in genes regulating renal development and podocyte function may respond to combination therapy with CyA and corticosteroids.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations

et al. 2010

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“…The WT1 mutation c.1372C>T (p.Arg458*) found in our patient results in truncation of the protein. This mutation has already been described as disease causing by others [5,6,8,9,10] and arginine at this position is highly conserved in evolution, which makes the pathogenicity of the mutation very likely.…”

Section: Discussionmentioning

confidence: 99%

Truncating <b><i>Wilms Tumor Suppressor Gene 1</i></b> Mutation in an XX Female with Adult-Onset Focal Segmental Glomerulosclerosis and Streak Ovaries: A Case Report

Hoefele

Kemper²,

Schoenermarck³

et al. 2016

Nephron

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About 30% of children with nephrotic syndrome (NS) have inherited forms. Among them, mutations in Wilms tumor suppressor gene 1 (WT1) are a well characterized cause associated with steroid-resistant NS, Wilms tumor, and urogenital malformation in males. However, the role of WT1 mutations in adult-onset focal segmental glomerulosclerosis (FSGS) is unclear. We report the case of a 38-year-old female with FSGS. She had been diagnosed with streak ovaries during diagnostic workup for infertility. Mutational analysis identified the heterozygous mutation c.1372C>T (p.Arg458*) in WT1 and the heterozygous non-neutral polymorphism c.868G>A (p.Arg229Gln) in NPHS2. Chromosomal analysis revealed a normal 46,XX female karyotype. Our case highlights that WT1 mutations should be considered in XX females with adult-onset FSGS, especially if urogenital abnormalities are present.

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“…Recently, a female patient with DDS was reported to have membranoproliferative glomerulonephritis type 1 (MPGN) in the native kidneys [4]. She underwent successful renal transplantation without evidence of recurrence of MPGN up to 4 years after transplantation.…”

Section: Introductionmentioning

confidence: 99%

Recurrence of membranoproliferative glomerulonephritis after renal transplantation in Denys–Drash

et al. 2010

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Denys-Drash syndrome (DDS) consists of the triad of nephropathy, male pseudohermaphroditism, and Wilms tumor caused by mutations within exons 8 or 9 of the Wilms tumor suppressor gene 1. Early onset nephrotic syndrome progresses to end-stage renal failure. The characteristic histological lesion is diffuse mesangial sclerosis. Here, we report on a boy with DDS who presented early with diffuse mesangial sclerosis, but subsequently also developed immune complex glomerulonephritis with a membranoproliferative pattern (MPGN-pattern GN) in his native kidneys. Four years after renal transplantation, immune complex glomerulonephritis with an MPGN pattern recurred in the renal graft resulting in proteinuria and progressive renal insufficiency.

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Membranoproliferative glomerulonephritis associated with a mutation in Wilms’ tumour suppressor gene 1

Cited by 10 publications

References 13 publications

Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations

Successful treatment of steroid-resistant nephrotic syndrome associated with WT1 mutations

Truncating <b><i>Wilms Tumor Suppressor Gene 1</i></b> Mutation in an XX Female with Adult-Onset Focal Segmental Glomerulosclerosis and Streak Ovaries: A Case Report

Recurrence of membranoproliferative glomerulonephritis after renal transplantation in Denys–Drash

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