A homozygous mutation in INVS causing juvenile nephronophthisis with abnormal reactivity of the Wnt/beta-catenin pathway

Nephrol Dial Transplant. 2010 Dec;25(12):4097-102. doi: 10.1093/ndt/gfq519. Epub 2010 Aug 26.

Abstract

Mutations in the INVS gene coding for inversin have been identified in patients with nephronophthisis type 2 (NPHP2), typically causing infantile onset of ESRD and potentially associated with situs inversus. We report a novel family with a homozygous INVS mutation (c.2695 C > T; p.Arg899X) deleting the C-terminus of inversin. Both affected patients had juvenile ESRD and were discordant for situs inversus. The end-stage kidneys showed chronic interstitial nephritis with cysts and abnormal expression of β-catenin and Dishevelled-1 supporting up-regulated canonical Wnt pathway in tubular cells. This case shows that INVS mutation can cause juvenile nephronophthisis with abnormal reactivity of the Wnt/β-catenin pathway.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Codon, Nonsense / genetics*
  • Dishevelled Proteins
  • Female
  • Homozygote*
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases, Cystic / congenital
  • Kidney Diseases, Cystic / genetics
  • Kidney Diseases, Cystic / surgery
  • Kidney Transplantation
  • Male
  • Pedigree
  • Phosphoproteins / metabolism
  • Signal Transduction / physiology*
  • Transcription Factors / genetics*
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Codon, Nonsense
  • DVL1 protein, human
  • Dishevelled Proteins
  • INVS protein, human
  • Phosphoproteins
  • Transcription Factors
  • Wnt Proteins
  • beta Catenin

Supplementary concepts

  • Nephronophthisis, familial juvenile