2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: ASN.2007020243v1 18/10/2789    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hoefele, J. Articles by Hildebrandt, F. Search for Related Content PubMed PubMed Citation Articles by Hoefele, J. Articles by Hildebrandt, F. Related Collections Related Article

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 and Friedhelm Hildebrandt^*,||

Departments of ^* Pediatrics and ^|| Human Genetics, University of Michigan, Ann Arbor, Michigan; Department of Pediatrics, University Children's Hospital, University of Munich, Munich, Germany; and Hôpital Robert Debré, Pediatric Nephrology, AP-HP, and INSERM, U574, Université Paris Descartes, Faculte de Médicine René Descartes, and Hôpital Necker-Enfants Malades, AP-HP, Department of Genetics, Paris, France

Correspondence: Dr. Friedhelm Hildebrandt, University of Michigan Health System, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0646. Phone: 734-615-7285; Fax: 734-615-1386; E-mail: fhilde{at}umich.edu

Received for publication September 27, 2006. Accepted for publication June 2, 2007.

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.

Related Article

This Month's Highlights
J. Am. Soc. Nephrol. 2007 18: A13. [Full Text] [PDF]

This article has been cited by other articles:

				S.-T. Jiang, Y.-Y. Chiou, E. Wang, H.-K. Lin, S.-P. Lee, H.-Y. Lu, C.-K. L. Wang, M.-J. Tang, and H. Li Targeted disruption of Nphp1 causes male infertility due to defects in the later steps of sperm morphogenesis in mice Hum. Mol. Genet., November 1, 2008; 17(21): 3368 - 3379. [Abstract] [Full Text] [PDF]

				K. V. Lemley Yet More Ways to Skin a Cat: Nephrin Mutations outside the Neonatal Period J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1837 - 1838. [Full Text] [PDF]

				A. R. Jauregui, K. C.Q. Nguyen, D. H. Hall, and M. M. Barr The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure J. Cell Biol., March 5, 2008; 180(5): 973 - 988. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673