Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease

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-o...

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Bibliographic Details
Published in:American journal of human genetics 2001-01, Vol.68 (1), p.219-224
Main Authors: Bingham, C, Bulman, M P, Ellard, S, Allen, L I, Lipkin, G W, Hoff, W G, Woolf, A S, Rizzoni, G, Novelli, G, Nicholls, A J, Hattersley, A T
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age of Onset
Blood Pressure
Child
Codon, Nonsense - genetics
Creatine - metabolism
Diabetes Complications
Diabetes Mellitus - epidemiology
Diabetes Mellitus - genetics
DNA Mutational Analysis
DNA-Binding Proteins - genetics
Exons - genetics
Female
Frameshift Mutation - genetics
Genetic Heterogeneity
Glucose Intolerance - complications
Glucose Intolerance - epidemiology
Glucose Intolerance - genetics
Hepatocyte Nuclear Factor 1-beta
Humans
Infant
Infant, Newborn
Kidney Diseases, Cystic - complications
Kidney Diseases, Cystic - epidemiology
Kidney Diseases, Cystic - genetics
Kidney Diseases, Cystic - metabolism
Male
Middle Aged
Mutation - genetics
Pedigree
Syndrome
Transcription Factors - genetics
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Summary: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.
ISSN:0002-9297