title: Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease.
abstract: Familial glomerulocystic kidney disease (GCKD) is a dominantly inherited condition characterized by glomerular cysts and variable renal size and function; the molecular genetic etiology is unknown. Mutations in the gene encoding hepatocyte nuclear factor (HNF)-1beta have been associated with early-onset diabetes and nondiabetic renal disease-particularly renal cystic disease. We investigated a possible role for the HNF-1beta gene in four unrelated GCKD families and identified mutations in two families: a nonsense mutation in exon 1 (E101X) and a frameshift mutation in exon 2 (P159fsdelT). The family members with HNF-1beta gene mutations had hypoplastic GCKD and early-onset diabetes or impaired glucose tolerance. We conclude that there is genetic heterogeneity in familial GCKD and that the hypoplastic subtype is a part of the clinical spectrum of the renal cysts and diabetes syndrome that is associated with HNF-1beta mutations.
authors.affiliation: Department of Vascular Medicine and Diabetes Research, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, EX2 5AX, Devon, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Bingham
authors.forename: M P
authors.initials: MP
authors.lastname: Bulman
authors.forename: S
authors.initials: S
authors.lastname: Ellard
authors.forename: L I
authors.initials: LI
authors.lastname: Allen
authors.forename: G W
authors.initials: GW
authors.lastname: Lipkin
authors.forename: W G
authors.initials: WG
authors.lastname: Hoff
authors.forename: A S
authors.initials: AS
authors.lastname: Woolf
authors.forename: G
authors.initials: G
authors.lastname: Rizzoni
authors.forename: G
authors.initials: G
authors.lastname: Novelli
authors.forename: A J
authors.initials: AJ
authors.lastname: Nicholls
authors.forename: A T
authors.initials: AT
authors.lastname: Hattersley
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001794:Blood Pressure; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics; D003401:Creatine / Q000378:metabolism; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D018740:Genetic Heterogeneity; D018149:Glucose Intolerance / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D052177:Kidney Diseases, Cystic / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; C496495:HNF1B protein, human; D014157:Transcription Factors; D051539:Hepatocyte Nuclear Factor 1-beta; D003401:Creatine