title: Assessment of the HNF1B Score as a Tool to Select Patients for HNF1B Genetic Testing.
abstract: OBJECTIVE
  Diagnosing hepatocyte nuclear factor 1β (HNF1B)-related disease is a challenging task due to the phenotypic variability and frequent absence of a family history. An HNF1B score has recently been developed to help select appropriate patients for genetic testing with a negative predictive value (NPV) of 99%. We aimed at testing the clinical utility of this score in a large number of referrals for HNF1B genetic testing to the UK diagnostic testing service for the HNF1B gene.
  
  
  METHODS
  An HNF1B score was assigned for 686 UK referrals for HNF1B genetic testing using clinical information available at referral. The performance of the score was evaluated by receiver-operating characteristic curve analysis. The relative discriminatory ability of different clinical features for making a genetic diagnosis of HNF1B-related disease were estimated in the UK dataset alone and pooled with French data.
  
  
  RESULTS
  The HNF1B score discriminated between patients with and without a mutation reasonably well with an area under the curve of 0.72. Applying the suggested cut-off score of ≥8 gave a NPV of 85%. In a pooled analysis, antenatal renal abnormalities, renal hyperechogenicity and cysts were discriminatory in children, whereas renal hypoplasia and cysts were discriminatory in adults. Pancreatic abnormalities were discriminatory in both, whereas other extra-renal characteristics had a large effect size only in adults.
  
  
  CONCLUSIONS
  The HNF1B score was discriminatory for HNF1B mutations in a large cohort of individuals tested in a single UK centre. The lower NPV (85 vs. 99%) reduces its clinical utility in selecting patients for HNF1B genetic testing, although validation in a prospective cohort is required.
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
authors.forename: Rhian
authors.initials: R
authors.lastname: Clissold
authors.forename: Beverley
authors.initials: B
authors.lastname: Shields
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Andrew
authors.initials: A
authors.lastname: Hattersley
authors.forename: Coralie
authors.initials: C
authors.lastname: Bingham
mesh_terms: D015331:Cohort Studies; D005820:Genetic Testing; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D009154:Mutation
chemical_list: C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta