title: [HNF1B-related disease: paradigm of a developmental gene and unexpected recognition of a new renal disease].
abstract: HNF1B encodes for a transcription factor involved in the early development of the kidney, pancreas, liver and genital tract. Mutations in HNF1B are dominantly inherited and consist of whole-gene deletion, or small mutation. De novo mutation occurs in half of tested kindreds. HNF1B-related disease combines renal and non-renal manifestations. Renal involvement is heterogeneous and may escape early recognition. During fetal life and childhood, it mostly consists of hyperechogenic kidneys or bilateral renal cystic hypodysplasia. The adult phenotype encompasses tubulointerstitial profile at presentation and slowly progressive renal decline (-2 ml/min/year). Renal involvement includes renal cysts (mostly few cortical cysts), a solitary kidney, pelvi-caliceal abnormalities, hypokalemia and hypomagnesemia related to tubular leak, and more rarely, Fanconi syndrome and chromophobe renal carcinoma. The latter warrants ultrasound screening. Extrarenal phenotype consists of diabetes mellitus (MODY-5), exocrine pancreas failure and pancreas atrophy; fluctuation liver tests abnormalities; diverse genital tract abnormalities in females or infertility in males; and mild mental retardation in rare individuals. Phenotype heterogeneity within families is striking. Individuals progressing to end-stage renal disease are eligible for kidney transplantation (or combined pancreas and kidney transplantation for diabetic individuals). While HNF1B disease was still unknown one decade ago, it has emerged as the second most prevalent dominantly inherited kidney disease. Data available pave the way for early recognition and improved specific management, including genetic counselling.
authors.affiliation: Service de néphrologie et immunologie clinique, CHU de Rangueil, 31059 Toulouse cedex 09, France; Inserm U1048, (I2MR, équipe 12), CHU de Rangueil, 31059 Toulouse cedex 09, France; Département de néphrologie et transplantation d'organes, centre de référence des maladies rénales rares du Sud-Ouest, CHU de Rangueil, 1, avenue Jean-Poulhès, TSA 50032, 31059 Toulouse cedex 9, France. Electronic address: chauveau.d@chu-toulouse.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Chauveau
authors.forename: Stanislas
authors.initials: S
authors.lastname: Faguer
authors.forename: Flavio
authors.initials: F
authors.lastname: Bandin
authors.forename: Vincent
authors.initials: V
authors.lastname: Guigonis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
authors.forename: Stéphane
authors.initials: S
authors.lastname: Decramer
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D008107:Liver Diseases / Q000235:genetics; D009154:Mutation; D010182:Pancreatic Diseases / Q000235:genetics; D014564:Urogenital Abnormalities / Q000235:genetics
chemical_list: D051539:Hepatocyte Nuclear Factor 1-beta
keywords: Developmental disorder; HNF1B; Hypokalemia; Hypomagnesemia; Hypomagnésémie; Inherited disease; Maladie du développement; Maladie héréditaire; Nephropathy; Néphropathie hypokaliémie