title: De novo HNF-1 beta gene mutation in familial hypoplastic glomerulocystic kidney disease.
abstract: Mutations in the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1 beta are associated with maturity-onset diabetes of the young (type V), non-diabetic renal disease, and occasionally genital malformations in females. Recently, familial hypoplastic glomerulocystic kidney disease (GCKD) has been added to the clinical spectrum of HNF-1 beta gene mutations. Familial hypoplastic GCKD is a rare, dominantly inherited disorder characterized by small kidneys containing glomerular cysts, abnormal pelvicalyceal anatomy, and chronic renal failure. A family with hypoplastic GCKD occurring in the father and the daughter was screened for mutations in the HNF-1 beta gene. The sequence of exon 4 of the HNF-1 beta gene revealed a C insertion at codon 334 resulting in a frameshift mutation (P334fsinsC) in two family members. The P334fsinsC allele co-segregated with hypoplastic GCKD in the family. Oral glucose tolerance testing was normal in the 11-year-old girl. In her 38-year-old father, impaired glucose tolerance was detected. These studies provide further evidence that familial hypoplastic GCKD is associated with HNF-1 beta gene mutations. HNF-1 beta gene mutation screening may prove useful in patients with small cystic kidneys and chronic renal failure, in whom a definite renal diagnosis could otherwise only be established by renal biopsy.
authors.affiliation: Department of Pediatrics, Graz University Medical School, Auenbruggerplatz 30, 8036 Graz, Styria, Austria. Christoph.mache@kfunigraz.ac.at
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Mache
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Preisegger
authors.forename: Susanne
authors.initials: S
authors.lastname: Kopp
authors.forename: Manfred
authors.initials: M
authors.lastname: Ratschek
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Ring
mesh_terms: D001317:Austria; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000235:genetics; D007678:Kidney Glomerulus / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D009687:Nuclear Proteins; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014463:Ultrasonography
chemical_list: D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D004247:DNA