Abstract
Aims/hypothesis. Maturity-onset diabetes of the young is an autosomal dominant form of diabetes characterised by an early age of onset (usually <25 years). We investigated the prevalence and trans-activating activity of hepatocyte nuclear factor (HNF)-1 α mutations in southern Chinese families with MODY.
Methods. We screened for mutations in the HNF-1 α gene in 50 unrelated southern Chinese families, which fulfilled the minimum criteria for MODY. Functional properties of the mutant proteins were investigated using site-directed mutagenesis and luciferase reporter assay.
Results. Five of the 50 (10%) families were found to have mutations in the coding region, including a new nonsense mutation Q176X and four reported mutations (frameshift mutation P379fsdelCT, nonsense mutation R171X, missense mutations G20R and P112L). These mutations had decreased trans-activating activity on the human insulin gene promoter. We also detected a new intronic sequence variation IVS7nt–6 G→A, which co-segregated with diabetes. The intronic variation creates a potential splice acceptor site and might alter the splicing of the HNF-1 α mRNA.
Conclusion/interpretation. Mutations in the HNF-1 α gene seem to be an important cause of MODY in southern Chinese. The mutations could affect normal islet function by altering the expression of target genes.
Article PDF
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Electronic Publication
Rights and permissions
About this article
Cite this article
Xu, J., Chan, V., Zhang, W. et al. Mutations in the hepatocyte nuclear factor-1α gene in Chinese MODY families: prevalence and functional analysis. Diabetologia 45, 744–746 (2002). https://doi.org/10.1007/s00125-002-0814-9
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00125-002-0814-9