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Gene locus ambiguity in posterior urethral valves/prune-belly syndrome

Pediatric Nephrology volume 20, pages 1036–1042 (2005)Cite this article

Abstract

Lower urinary tract obstruction by posterior urethral valves (PUV) is an important cause of congenital renal failure in male infants. Though population-based studies point to a role of genetic factors in the etiology of PUV, no clear evidence for a specific gene defect for PUV has been observed so far. Here we present a consanguineous family with four male descendants affected by PUV and a healthy girl, suggestive of autosomal recessive inheritance. One boy presented with prune-belly syndrome (PBS) in addition to PUV. Using a DNA chip-based genome-wide linkage analysis, we identified a region of homozygosity for the affected boys in an interval of 35 cM on chromosome 1q41–44 with a maximum multipoint LOD score of Zmax=3.134 at θ=0 for single nucleotide polymorphisms (SNPs) rs158724-rs720163. By applying a second genetic model based on the assumption of a male-limited phenotype and the girl being carrier of the genetic defect without expressing the phenotype, a second alternative locus of 9 cM on chromosome 11p11 was identified with a LOD score of Zmax=3.61 at θ=0. Equal significance for both loci with a LOD score of Zmax=3.01 at θ = 0 was obtained after the affection status of the female descendant was set “unknown”. We suppose that most probably, only one of the two identified loci harbours the disease-causing gene. As the interpretation of the girl’s status remains uncertain, we are not able to exclude one of the two loci. Analyses of additional informative families will be important to exclude one of the two loci and to restrict the critical interval.

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Acknowledgements

We thank the patients and their family for participating in this study. S.W. was supported by the Deutsche Forschungsgemeinschaft (WE 2724/2–2). The Berlin Gene Mapping Center is funded by the German Federal Ministry of Science and Education through the National Genome Research Network (NGFN, grant 01GR0104)

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Affiliations

  1. Pediatric Nephrology, University Children’s Hospital Heidelberg, Im Neuenheimer Feld 150, 69120, Heidelberg, Germany

    Stefanie Weber & Franz Schaefer

  2. Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey

    Sevgi Mir, Pelin E. Kara & Nese Ozkayin

  3. Department of Pediatrics, University Children’s Hospital, Marburg, Germany

    Karl Peter Schlingmann

  4. Gene Mapping Center, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany

    Gudrun Nürnberg, Christian Becker & Peter Nürnberg

  5. Pediatric Nephrology, Inselspital, Bern, Switzerland

    Martin Konrad

  6. Institute of Medical Genetics, Charité - University of Medicine Berlin, Berlin, Germany

    Peter Nürnberg

Authors
  1. Stefanie Weber
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  2. Sevgi Mir
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  3. Karl Peter Schlingmann
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  4. Gudrun Nürnberg
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  5. Christian Becker
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  6. Pelin E. Kara
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  7. Nese Ozkayin
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  8. Martin Konrad
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  9. Peter Nürnberg
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  10. Franz Schaefer
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Correspondence to Stefanie Weber.

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Weber, S., Mir, S., Schlingmann, K.P. et al. Gene locus ambiguity in posterior urethral valves/prune-belly syndrome. Pediatr Nephrol 20, 1036–1042 (2005). https://doi.org/10.1007/s00467-005-1977-7

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  • DOI: https://doi.org/10.1007/s00467-005-1977-7

Keywords

  • Posterior urethral valves
  • PUV
  • Prune-belly syndrome
  • Linkage analysis
  • Mapping
  • Autosomal recessive inheritance
  • Male-limited phenotype