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

Pediatr Nephrol. 2009 Jan;24(1):55-60. doi: 10.1007/s00467-008-1016-6. Epub 2008 Oct 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Male
  • Mucoproteins / genetics*
  • Mutation*
  • Urinary Tract / abnormalities*
  • Urologic Diseases / congenital*
  • Urologic Diseases / genetics*
  • Uromodulin
  • Young Adult

Substances

  • Mucoproteins
  • UMOD protein, human
  • Uromodulin