title: Criteria for HNF1B analysis in patients with congenital abnormalities of kidney and urinary tract.
abstract: BACKGROUND
  Congenital anomalies of kidneys and urinary tract (CAKUT) are the most predominant developmental disorders comprising ∼20-30% of all anomalies identified in the prenatal period. Mutations in hepatocyte nuclear factor 1-beta (HNF-1β) involved in the development of kidneys, liver, pancreas and urogenital tract are currently the most frequent monogenetic cause of CAKUT found in 10-30% of patients depending on screening policy and study design. We aimed to validate criteria for analysis of HNF1B in a prospective cohort of paediatric and adult CAKUT patients.
  
  
  METHODS
  We included CAKUT patients diagnosed in our paediatric and adult nephrology departments from January 2010 until April 2013 based on predefined screening criteria. Subjects presenting with at least one major renal criterion or one minor renal criterion combined with one or more extra-renal criteria in the personal history or a familial history of renal or extra-renal manifestations were considered eligible.
  
  
  RESULTS
  We prospectively screened 205 patients and detected HNF1B mutations in 10% [n = 20, 12 children, median age 4.2 (range 0-13.1) years and 8 adults, median age 34.8 (range 16.6-62) years]. We observed that bilateral renal anomaly, renal cysts from unknown origin, a combination of two major renal anomalies and hypomagnesaemia were predictive for finding HNF1B mutations (P < 0.001; P < 0.001; P = 0.004; P = 0.008, respectively).
  
  
  CONCLUSIONS
  We demonstrated that HNF1B mutations are responsible for ∼10% of CAKUT cases, both in children and in adults. Based on our results we propose adapted criteria for HNF1B analysis to reduce the screening costs without missing affected patients. These criteria should be reaffirmed in a larger validation cohort.
authors.affiliation: Department of Pediatric Nephrology, UZ Leuven, Leuven, Belgium.
authors.forename: Anke
authors.initials: A
authors.lastname: Raaijmakers
authors.affiliation: Department of Human Genetics, UZ Leuven/KU Leuven, Leuven, Belgium.
authors.forename: Anniek
authors.initials: A
authors.lastname: Corveleyn
authors.affiliation: Department of Human Genetics, UZ Leuven/KU Leuven, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.affiliation: Department of Sociology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Theun Pieter
authors.initials: TP
authors.lastname: van Tienoven
authors.affiliation: Neonatal Intensive Care Unit, UZ Leuven, Leuven, Belgium.
authors.forename: Karel
authors.initials: K
authors.lastname: Allegaert
authors.affiliation: Department of Pediatric Nephrology, UZ Leuven, Leuven, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Van Dyck
authors.affiliation: Department of Pediatric Nephrology, UZ Leuven, Leuven, Belgium.
authors.forename: Lambertus
authors.initials: L
authors.lastname: van den Heuvel
authors.affiliation: Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Kuypers
authors.affiliation: Department of Nephrology, UZ Leuven, Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Claes
authors.affiliation: Department of Pediatric Nephrology, UZ Leuven, Leuven, Belgium.
authors.forename: Djalila
authors.initials: D
authors.lastname: Mekahli
authors.affiliation: Department of Pediatric Nephrology, UZ Leuven, Leuven, Belgium.
authors.forename: Elena
authors.initials: E
authors.lastname: Levtchenko
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000002:abnormalities*; D007674:Kidney Diseases / Q000235:genetics*; D052177:Kidney Diseases, Cystic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D014551:Urinary Tract / Q000002:abnormalities*; D014570:Urologic Diseases / Q000235:genetics*; D055815:Young Adult
chemical_list: C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta
keywords: CAKUT; HNF1β; genetic screening; hepatocyte nuclear factor 1-beta; renal development