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) All Versions of this Article: ASN.2006030277v1 17/10/2864    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 Weber, S. Articles by Salomon, R. Search for Related Content PubMed PubMed Citation Articles by Weber, S. Articles by Salomon, R.

Prevalence of Mutations in Renal Developmental Genes in Children with Renal Hypodysplasia: Results of the ESCAPE Study

Stefanie Weber^*,, Vincent Moriniere, Tanja Knüppel^*, Marina Charbit, Jirí Dusek, Gian Marco Ghiggeri^||, Augustina Jankauskiené^¶, Sevgi Mir^**, Giovanni Montini, Amira Peco-Antic, Elke Wühl^*, Aleksandra M. Zurowska, Otto Mehls^*, Corinne Antignac, Franz Schaefer^* and Remi Salomon^,

^* Division of Pediatric Nephrology, Hospital for Pediatric and Adolescent Medicine, Ruperto-Carola University, Heidelberg, Germany; Inserm U574 and Pediatric Nephrology, Hôpital Necker-Enfants Malades, Université René Descartes, Paris, France; Motol Children’s Hospital Prague, Czech Republic; ^|| Istituto Gaslini, Genoa, Italy; ^¶ University Children’s Hospital, Vilnius, Lithuania; ^** University Children’s Hospital, Izmir, Turkey; Division of Pediatric Nephrology, Children’s Hospital, University of Padova, Padova, Italy; University Children’s Hospital Belgrade, Serbia and Herzegovina; and University Children’s Hospital, Gdansk, Poland

Address correspondence to: Dr. Rémi Salomon, Department of Pediatric Nephrology, Hôpital Necker-Enfants Malades, Université René Descartes, 147, Rue de Sèvres, 75015 Paris, France. Phone: +33-1-444-94-462; Fax: +33-1-444-94-460; E-mail: salomon{at}necker.fr

Received for publication March 26, 2006. Accepted for publication August 2, 2006.

Renal hypodysplasia (RHD) is characterized by a reduced nephron number, small kidney size, and disorganized renal tissue. A hereditary basis has been established for a subset of affected patients, suggesting a major role of developmental genes that are involved in early kidney organogenesis. Gene mutations that have dominant inheritance and cause RHD, urinary tract anomalies, and defined extrarenal symptoms have been identified in TCF2 (renal cysts and diabetes syndrome), PAX2 (renal-coloboma syndrome), EYA1 and SIX1 (branchio-oto-renal syndrome), and SALL1 (Townes-Brocks syndrome). For estimation of the prevalence of these events, an unselected cohort of 99 unrelated patients with RHD that was associated with chronic renal insufficiency were screened for mutations in TCF2, PAX2, EYA1, SIX1, and SALL1. Mutations or variants in the genes of interest were detected in 17 (17%) unrelated families: One mutation, two variants, and four deletions of TCF2 in eight unrelated patients; four different PAX2 mutations in six families; one EYA1 mutation and one deletion in two patients with branchio-oto-renal syndrome; and one SALL1 mutation in a patient with isolated RHD. Of a total of 27 patients with renal cysts, six (22%) carried a mutation in TCF2. It is interesting that a SIX1 sequence variant was identified in two siblings with renal-coloboma syndrome as a result of a PAX2 mutation, suggesting an oligogenic inheritance. Careful clinical reevaluation that focused on discrete extrarenal symptoms and thorough family analysis revealed syndrome-specific features in nine of the 17 patients. In conclusion, 15% of patients with RHD show mutations in TCF2 or PAX2, whereas abnormalities in EYA1, SALL1, and SIX1 are less frequent.

This article has been cited by other articles:

				Z. Ma, Y. Gong, V. Patel, C. M. Karner, E. Fischer, T. Hiesberger, T. J. Carroll, M. Pontoglio, and P. Igarashi Mutations of HNF-1 inhibit epithelial morphogenesis through dysregulation of SOCS-3 PNAS, December 18, 2007; 104(51): 20386 - 20391. [Abstract] [Full Text] [PDF]

				E. Benetti, L. Artifoni, L. Salviati, L. Pinello, S. Perrotta, O. Zuffardi, G. Zacchello, and L. Murer Renal hypoplasia without optic coloboma associated with PAX2 gene deletion Nephrol. Dial. Transplant., July 1, 2007; 22(7): 2076 - 2078. [Full Text] [PDF]

				C. Carette, C. Vaury, A. Barthelemy, S. Clauin, J.-P. Grunfeld, J. Timsit, and C. Bellanne-Chantelot Exonic Duplication of the Hepatocyte Nuclear Factor-1{beta} Gene (Transcription Factor 2, Hepatic) as a Cause of Maturity Onset Diabetes of the Young Type 5 J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2844 - 2847. [Abstract] [Full Text] [PDF]

				S. Decramer, O. Parant, S. Beaufils, S. Clauin, C. Guillou, S. Kessler, J. Aziza, F. Bandin, J. P. Schanstra, and C. Bellanne-Chantelot Anomalies of the TCF2 Gene Are the Main Cause of Fetal Bilateral Hyperechogenic Kidneys J. Am. Soc. Nephrol., March 1, 2007; 18(3): 923 - 933. [Abstract] [Full Text] [PDF]

				A. S. Woolf Renal Hypoplasia and Dysplasia: Starting to Put the Puzzle Together J. Am. Soc. Nephrol., October 1, 2006; 17(10): 2647 - 2649. [Full Text] [PDF]

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