title: Diagnosis, management, and prognosis of HNF1B nephropathy in adulthood.
abstract: Mutations in HNF1B are responsible for a dominantly inherited disease with renal and nonrenal consequences, including maturity-onset diabetes of the young (MODY) type 5. While HNF1B nephropathy is typically responsible for bilateral renal cystic hypodysplasia in childhood, the adult phenotype is poorly described. To help define this we evaluated the clinical presentation, imaging findings, genetic changes, and disease progression in 27 adults from 20 families with HNF1B nephropathy. Whole-gene deletion was found in 11 families, point mutations in 9, and de novo mutations in half of the kindred tested. Renal involvement was extremely heterogeneous, with a tubulointerstitial profile at presentation and slowly progressive renal decline throughout adulthood as hallmarks of the disease. In 24 patients tested, there were cysts (≤5 per kidney) in 15, a solitary kidney in 5, hypokalemia in 11, and hypomagnesemia in 10 of 16 tested, all as characteristics pointing to HNF1B disease. Two patients presented with renal Fanconi syndrome and, overall, 4 progressed to end-stage renal failure. Extrarenal phenotypes consisted of diabetes mellitus in 13 of the 27 patients, including 11 with MODY, abnormal liver tests in 8 of 21, diverse genital tract abnormalities in 5 of 13 females, and infertility in 2 of 14 males. Thus, our findings provide data that are useful for recognition and diagnosis of HNF1B disease in adulthood and might help in renal management and genetic counseling.
authors.affiliation: Service de Néphrologie et Immunologie clinique, Hôpital Rangueil, CHU Toulouse, France. stanislas.faguer@inserm.fr
authors.forename: Stanislas
authors.initials: S
authors.lastname: Faguer
authors.forename: Stéphane
authors.initials: S
authors.lastname: Decramer
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
authors.forename: Christine
authors.initials: C
authors.lastname: Bellanné-Chantelot
authors.forename: Patrick
authors.initials: P
authors.lastname: Calvas
authors.forename: Sandrine
authors.initials: S
authors.lastname: Beaufils
authors.forename: Lucie
authors.initials: L
authors.lastname: Bessenay
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lengelé
authors.forename: Karine
authors.initials: K
authors.lastname: Dahan
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.forename: Dominique
authors.initials: D
authors.lastname: Chauveau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D011379:Prognosis; D055815:Young Adult
chemical_list: C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta