A homozygous mutation in INVS causing juvenile nephronophthisis with abnormal reactivity of the Wnt/beta-catenin pathway.
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.
Bellavia
Salvatore
S
Division of Nephrology, Cliniques Universitaires St. Luc, Université catholique de Louvain, Bruxelles, Belgium.
Dahan
Karin
K
Terryn
Sara
S
Cosyns
Jean-Pierre
JP
Devuyst
Olivier
O
Pirson
Yves
Y
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D018389:Codon, Nonsense / Q000235:genetics*; D000072261:Dishevelled Proteins; D005260:Female; D006720:Homozygote; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D052177:Kidney Diseases, Cystic / Q000151:congenital / Q000235:genetics / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D010375:Pedigree; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018389:Codon, Nonsense; C000606578:DVL1 protein, human; D000072261:Dishevelled Proteins; C114503:INVS protein, human; D010750:Phosphoproteins; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin