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NDT Advance Access published online on September 10, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp453
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© The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Analysis of TSHZ2 and TSHZ3 genes in congenital pelvi-ureteric junction obstruction

Dagan Jenkins1, Xavier Caubit2, Aleksandar Dimovski3, Nadica Matevska3, Claire M. Lye4, Feryal Cabuk5, Zoran Gucev6, Velibor Tasic6, Laurent Fasano2 and Adrian S. Woolf7

1 Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK 2 Institut de Biologie du Développement de Marseille-Luminy (IBDML), UMR6216, CNRS, Université de la Méditerranée, F-13288 Marseille cedex 09, France 3 Department of Molecular Biology and Genetics, Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, Skopje, Macedonia 4 Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK 5 Department of Medical Biology and Genetics, Kirikkale University, Medical School, Kirikkale, Turkey 6 Department of Pediatric Nephrology, University Children's Hospital, Skopje, Macedonia 7 Nephro-Urology Unit, UCL Institute of Child Health, 30 Guilford Street, London, UK

Correspondence and offprint requests to: Dagan Jenkins; E-mail: dagan.jenkins{at}imm.ox.ac.uk



  Abstract

Background. Congenital pelvi-ureteric junction obstruction (PUJO) affects 0.3% of human births. It may result from aberrant smooth muscle development in the renal pelvis, resulting in hydronephrosis. Mice that are null mutant for the Teashirt3 (Tshz3) gene exhibit congenital PUJO with defective smooth muscle differentiation and absent peristalsis in the proximal ureter.

Methods. Given the phenotype of Tshz3 mutant mice, we considered that Teashirt genes, which code for a family of transcription factors, might represent candidate genes for human PUJO. To evaluate this possibility, we used in situ hydridization to analyse the three mammalian Tshz genes in mouse embryonic ureters and determined whether TSHZ3 was expressed in the human embryonic ureter. TSHZ2 and TSHZ3 were sequenced in index cases with non-syndromic PUJO.

Results. Tshz2 and Tshz3 genes were detected in mouse ureters and TSHZ3 was expressed in the human embryonic renal pelvis. Direct sequencing of TSHZ2 and TSHZ3 did not identify any mutations in an initial cohort of 48 PUJO index cases, excluding these genes as a major cause of this condition. A polymorphic missense change (E469G) in TSHZ3 was identified at a residue highly conserved throughout evolution in all Teashirt proteins, although subsequently no significant difference between the E469G allele frequency in Albanian and Macedonian PUJO index cases (3.2%) versus 633 control individuals (1.7%) was found (P = 0.18).

Conclusions. Mutations in TSHZ2 and TSHZ3 are not a major cause of PUJO, at least in Albanian and Macedonian populations. Expression of these genes in the human fetal ureter emphasizes the importance of analysing these genes in other groups of patients with renal tract malformations.

Keywords: pelvi-ureteric junction obstruction; Teashirt genes

Received for publication: 22.12.08
Accepted in revised form: 11. 8.09


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