title: Hepatocyte nuclear factor-1beta gene deletions--a common cause of renal disease.
abstract: BACKGROUND
  Hepatocyte nuclear factor-1beta (HNF-1beta) is a critical transcription factor in pancreatic and renal development. Our previous report identified HNF-1beta mutations in 23/160 patients with unexplained renal disease. The most common phenotype is renal cysts, which is frequently associated with early-onset diabetes in the renal cysts and diabetes (RCAD) syndrome. HNF-1beta gene deletions have recently been shown to cause renal malformations and early-onset diabetes.
  
  
  METHODS
  We developed a multiplex ligation-dependent probe amplification (MLPA) assay for HNF-1beta gene dosage analysis and tested patients with unexplained renal disease in whom mutations had not been found by sequencing.
  
  
  RESULTS
  Whole HNF-1beta gene deletions were detected in 15/133 probands. Renal cysts were present in 13/15, including three with glomerulocystic kidney disease and one with cystic renal dysplasia. Renal function ranged from normal to transplantation aged 3 years. Ten probands had diabetes (nine having RCAD). In addition, four had abnormal liver function tests, two showed pancreatic atrophy and 3/10 female probands had uterine malformations. Whole HNF-1beta gene deletions are a common cause of developmental renal disease, particularly renal cystic disease with or without diabetes.
  
  
  CONCLUSIONS
  The phenotype associated with deletions or coding region/splicing mutations is very similar suggesting that haploinsufficiency is the underlying mechanism. Patients with features suggestive of the HNF-1beta clinical phenotype should be tested for mutations both by sequence and dosage analysis.
authors.affiliation: 1Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Edghill
authors.forename: Richard A
authors.initials: RA
authors.lastname: Oram
authors.forename: Martina
authors.initials: M
authors.lastname: Owens
authors.forename: Karen L
authors.initials: KL
authors.lastname: Stals
authors.forename: Lorna W
authors.initials: LW
authors.lastname: Harries
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Coralie
authors.initials: C
authors.lastname: Bingham
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: D051539:Hepatocyte Nuclear Factor 1-beta