Evidence of oligogenic inheritance in nephronophthisis

Julia Hoefele, Matthias T F Wolf, John F. O'Toole, Edgar A. Otto, Ulla Schultheiss, Georges Dêschenes, Massimo Attanasio, Boris Utsch, Corinne Antignac, Friedhelm Hildebrandt

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


Nephronophthisis is a recessive cystic renal disease that leads to end-stage renal failure in the first two decades of life. Twenty-five percent of nephronophthisis cases are caused by large homozygous deletions of NPHP1, but six genes responsible for nephronophthisis have been identified. Because oligogenic inheritance has been described for the related Bardet-Biedl syndrome, we evaluated whether mutations in more than one gene may also be detected in cases of nephronophthisis. Because the nephrocystins 1 to 4 are known to interact, we examined patients with nephronophthisis from 94 different families and sequenced all exons of the NPHP1, NPHP2, NPHP3, and NPHP4 genes. In our previous studies involving 44 families, we detected two mutations in one of the NPHP1-4 genes. Here, we detected in six families two mutations in either NPHP1, NPHP3, or NPHP4, and identified a third mutation in one of the other NPHP genes. Furthermore, we found possible digenic disease by detecting one individual who carried one mutation in NPHP2 and a second mutation in NPHP3. Finally, we detected the presence of a single mutation in nine families, suggesting that the second recessive mutation may be in another as yet unidentified NPHP gene. Our findings suggest that oligogenicity may occur in cases of nephronophthisis.

Original languageEnglish (US)
Pages (from-to)2789-2795
Number of pages7
JournalJournal of the American Society of Nephrology
Issue number10
StatePublished - Oct 2007

ASJC Scopus subject areas

  • Nephrology


Dive into the research topics of 'Evidence of oligogenic inheritance in nephronophthisis'. Together they form a unique fingerprint.

Cite this