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Mutation analysis of the Uromodulin gene in 96 individuals with urinary tract anomalies (CAKUT)

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Abstract

Uromodulin (UMOD) mutations were described in patients with medullary cystic kidney disease (MCKD2), familial juvenile hyperuricemic nephropathy (FJHN), and glomerulocystic kidney disease (GCKD). UMOD transcription is activated by the transcription factor HNF1B. Mutations in HNF1B cause a phenotype similar to FJHN/GCKD but also congenital anomalies of the kidney and the urinary tract (CAKUT). Moreover, we recently detected UMOD mutations in two patients with CAKUT. As HNF1B and UMOD act in the same pathway and cause similar phenotypes, we here examined whether UMOD mutations would be found in patients with CAKUT. Mutation analysis of UMOD was performed in 96 individuals with CAKUT by direct sequencing of exons 4 and 5 and by heteroduplex analysis following CEL I digestion assay of exons 3 and 6–12. Mean patient age was 11.4 years, and in 36.4% of patients, family history was positive for CAKUT. In the CEL I assay, 12 aberrant bands were detected in 103 of 960 polymerase chain reaction (PCR) products and were sequenced. Six previously known and seven new single nucleotide polymorphisms (SNPs) were detected. As no UMOD mutations were identified in these 96 patients with CAKUT, UMOD mutations do not seem to be a significant cause of CAKUT in this cohort.

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Acknowledgements

We thank all individuals who participated in this study. The technical assistance of Steffi Schneider is gratefully acknowledged. FH is the Frederick G.L. Huetwell professor and a Doris Duke Distinguished Clinical Scientist. He is supported by grants from the NIH (DK068306, DK064614 and DK069274). MTFW was supported by grants from the Koeln Fortune Program Faculty of Medicine, University of Cologne (184/2004), the German Kidney Fund (Deutsche Nierenstiftung), and the German Research Foundation (DFG WO 1229/2-1).

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Authors and Affiliations

  1. Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA

    Matthias T. F. Wolf, Bethan E. Hoskins, Edgar A. Otto & Friedhelm Hildebrandt

  2. Children’s Medical Center of Dallas, University of Texas, Southwestern Medical Center, Dallas, TX, USA

    Matthias T. F. Wolf

  3. Department of Pediatric Nephrology of the University Children’s Hospital, University of Cologne, Cologne, Germany

    Matthias T. F. Wolf, Bodo B. Beck & Bernd Hoppe

  4. Department of Pediatric Nephrology, Clinic for Children’s Diseases, Medical School Skopje, Skopje, Macedonia

    Velibor Tasic

  5. Department of Human Genetics, University of Michigan, Ann Arbor, USA

    Friedhelm Hildebrandt

  6. Department of Pediatrics and Communicable Diseases, University of Michigan, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI, 48109-5646, USA

    Friedhelm Hildebrandt

Authors
  1. Matthias T. F. Wolf
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  2. Bethan E. Hoskins
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  3. Bodo B. Beck
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  4. Bernd Hoppe
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  5. Velibor Tasic
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  6. Edgar A. Otto
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  7. Friedhelm Hildebrandt
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Correspondence to Friedhelm Hildebrandt.

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Wolf, M.T.F., Hoskins, B.E., Beck, B.B. et al. Mutation analysis of the Uromodulin gene in 96 individuals with urinary tract anomalies (CAKUT). Pediatr Nephrol 24, 55–60 (2009). https://doi.org/10.1007/s00467-008-1016-6

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  • DOI: https://doi.org/10.1007/s00467-008-1016-6

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