title: A homozygous mutation in INVS causing juvenile nephronophthisis with abnormal reactivity of the Wnt/beta-catenin pathway.
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.
authors.affiliation: Division of Nephrology, Cliniques Universitaires St. Luc, Université catholique de Louvain, Bruxelles, Belgium.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Bellavia
authors.forename: Karin
authors.initials: K
authors.lastname: Dahan
authors.forename: Sara
authors.initials: S
authors.lastname: Terryn
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cosyns
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.forename: Yves
authors.initials: Y
authors.lastname: Pirson
mesh_terms: 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*
chemical_list: 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