title: The HNF1B score is a simple tool to select patients for HNF1B gene analysis.
abstract: HNF1B-related disease is an emerging condition characterized by an autosomal-dominant inheritance, a 50% rate of de novo mutations, and a highly variable phenotype (renal involvement, maturity-onset diabetes of the young type 5, pancreatic hypoplasia, and urogenital tract and liver test abnormalities). Given the current lack of pathognomonic characteristics and the wide overlap with other conditions, a genetic test is the diagnostic gold standard. However, pre-genetic screening is mandatory because genetic testing has substantial costs. Our aim was to develop a HNF1B score, based on clinical, imaging, and biological variables, as a pivotal tool for rational genetic testing. A score was created using a weighted combination of the most discriminative characteristics based on the frequency and specificity in published series. The HNF1B score is calculated upon 17 items including antenatal discovery, family history, and organ involvement (kidney, pancreas, liver, and genital tract). The performance of the score was assessed by a ROC curve analysis in a 433-individual cohort containing 56 HNF1B cases. The HNF1B score efficiently and significantly discriminated between mutated and nonmutated cases (AUC 0.78). The optimal cutoff threshold for the negative predictive value to rule out HNF1B mutations in a suspected individual was 8 (sensitivity 98.2%, specificity 41.1%, and negative predictive value over 99%). Thus, the HNF1B score is a simple and accurate tool to provide a more rational approach to select patients for HNF1B screening.
authors.affiliation: 1] Département de Néphrologie et Transplantation d'organes, Hôpital Rangueil, CHU Toulouse, France [2] Centre de référence des maladies rénales rares, Toulouse, France [3] Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Cardiovascular and Metabolic Disease, Toulouse, France [4] Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Faguer
authors.affiliation: 1] Université Toulouse III Paul-Sabatier, Toulouse, France [2] Service de Génétique médicale et UPS III EA4555, Hôpital Purpan, CHU de Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
authors.affiliation: Centre de référence des maladies rénales rares, Toulouse, France.
authors.forename: Flavio
authors.initials: F
authors.lastname: Bandin
authors.affiliation: Centre de référence des maladies rénales rares, Toulouse, France.
authors.forename: Cathie
authors.initials: C
authors.lastname: Prouheze
authors.affiliation: Service de Néphrologie Pédiatrique, HTA et Médecine Interne, Hôpital des Enfants, CHU Toulouse, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Garnier
authors.affiliation: 1] Centre de référence des maladies rénales rares, Toulouse, France [2] Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Cardiovascular and Metabolic Disease, Toulouse, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Casemayou
authors.affiliation: Département de Néphrologie et Transplantation d'organes, Hôpital Rangueil, CHU Toulouse, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Huart
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Cardiovascular and Metabolic Disease, Toulouse, France [2] Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.affiliation: 1] Université Toulouse III Paul-Sabatier, Toulouse, France [2] Service de Génétique médicale et UPS III EA4555, Hôpital Purpan, CHU de Toulouse, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Calvas
authors.affiliation: 1] Centre de référence des maladies rénales rares, Toulouse, France [2] Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Cardiovascular and Metabolic Disease, Toulouse, France [3] Université Toulouse III Paul-Sabatier, Toulouse, France [4] Service de Néphrologie Pédiatrique, HTA et Médecine Interne, Hôpital des Enfants, CHU Toulouse, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Decramer
authors.affiliation: 1] Département de Néphrologie et Transplantation d'organes, Hôpital Rangueil, CHU Toulouse, France [2] Centre de référence des maladies rénales rares, Toulouse, France [3] Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institute of Cardiovascular and Metabolic Disease, Toulouse, France [4] Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Chauveau
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D004252:DNA Mutational Analysis; D003661:Decision Support Techniques; D003952:Diagnostic Imaging; D005602:France; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D040941:Heredity; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008111:Liver Function Tests; D009154:Mutation; D018579:Patient Selection; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta