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Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS).

Publication ,  Journal Article
Gbadegesin, R; Hinkes, BG; Hoskins, BE; Vlangos, CN; Heeringa, SF; Liu, J; Loirat, C; Ozaltin, F; Hashmi, S; Ulmer, F; Cleper, R; Ettenger, R ...
Published in: Nephrol Dial Transplant
April 2008

BACKGROUND AND OBJECTIVES: Diffuse mesangial sclerosis (DMS) is a histologically distinct variant of nephrotic syndrome (NS) that is characterized by early onset and by progression to end-stage kidney disease (ESKD). Besides syndromic DMS, isolated (non-syndromic) DMS (IDMS) has been described. The etiology and pathogenesis of DMS is not understood. We recently identified by positional cloning recessive mutations in the gene PLCE1/NPHS3 as a novel cause of IDMS. We demonstrated a role of PLCE1 in glomerulogenesis. Mutations in two other genes WT1 and LAMB2 may also cause IDMS. We therefore determine in this study the relative frequency of mutations in PLCE1, WT1 or LAMB2 as the cause of IDMS in a worldwide cohort. METHODS: We identified 40 children from 35 families with IDMS from a worldwide cohort of 1368 children with NS. All the subjects were analyzed for mutations in all exons of PLCE1 by multiplex capillary heteroduplex analysis and direct sequencing, by direct sequencing of exons 8 and 9 of WT1, and all the exons of LAMB2. RESULTS: The median (range) age at onset of NS was 11 (1-72) months. We detected truncating mutations in PLCE1 in 10/35 (28.6%) families and WT1 mutations in 3/35 (8.5%) families. We found no mutations in LAMB2. CONCLUSIONS: PLCE1 mutation is the most common cause of IDMS in this cohort. We previously reported that one child with truncating mutation in PLCE1 responded to cyclosporine therapy. If this observation is confirmed in a larger study, mutations in PLCE1 may serve as a biomarker for selecting patients with IDMS who may benefit from treatment.

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Published In

Nephrol Dial Transplant

DOI

EISSN

1460-2385

Publication Date

April 2008

Volume

23

Issue

4

Start / End Page

1291 / 1297

Location

England

Related Subject Headings

  • WT1 Proteins
  • Urology & Nephrology
  • Severity of Illness Index
  • Prognosis
  • Polymerase Chain Reaction
  • Phosphoinositide Phospholipase C
  • Nephrosclerosis
  • Mutation
  • Male
  • Laminin
 

Citation

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Gbadegesin, R., Hinkes, B. G., Hoskins, B. E., Vlangos, C. N., Heeringa, S. F., Liu, J., … Hildebrandt, F. (2008). Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrol Dial Transplant, 23(4), 1291–1297. https://doi.org/10.1093/ndt/gfm759
Gbadegesin, Rasheed, Bernward G. Hinkes, Bethan E. Hoskins, Christopher N. Vlangos, Saskia F. Heeringa, Jinhong Liu, Chantal Loirat, et al. “Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS).Nephrol Dial Transplant 23, no. 4 (April 2008): 1291–97. https://doi.org/10.1093/ndt/gfm759.
Gbadegesin R, Hinkes BG, Hoskins BE, Vlangos CN, Heeringa SF, Liu J, et al. Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrol Dial Transplant. 2008 Apr;23(4):1291–7.
Gbadegesin, Rasheed, et al. “Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS).Nephrol Dial Transplant, vol. 23, no. 4, Apr. 2008, pp. 1291–97. Pubmed, doi:10.1093/ndt/gfm759.
Gbadegesin R, Hinkes BG, Hoskins BE, Vlangos CN, Heeringa SF, Liu J, Loirat C, Ozaltin F, Hashmi S, Ulmer F, Cleper R, Ettenger R, Antignac C, Wiggins RC, Zenker M, Hildebrandt F. Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrol Dial Transplant. 2008 Apr;23(4):1291–1297.
Journal cover image

Published In

Nephrol Dial Transplant

DOI

EISSN

1460-2385

Publication Date

April 2008

Volume

23

Issue

4

Start / End Page

1291 / 1297

Location

England

Related Subject Headings

  • WT1 Proteins
  • Urology & Nephrology
  • Severity of Illness Index
  • Prognosis
  • Polymerase Chain Reaction
  • Phosphoinositide Phospholipase C
  • Nephrosclerosis
  • Mutation
  • Male
  • Laminin