A family with a novel termination mutation in hepatic nuclear factor 1α in maturity-onset diabetes of the young type 3 which is unresponsive to sulphonylurea therapy

S. Demol, Y. Lebenthal, M. Bar-Meisels, M. Phillip, G. Gat-Yablonski*, Y. Gozlan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus. Aims: To identify the genetic basis in a family with 3 generations of diabetes and to assess the concordance between the genotype and phenotype. Methods: A molecular analysis was performed on genomic DNA using polymerase chain reaction, denaturing gradient gel electrophoresis, and sequencing. A mixed-meal tolerance test (MMTT) was performed with/without glibenclamide. Abdominal ultrasonography was performed on all family members with diabetes due to the location of the mutation. Results: A novel c.618G>A, p.W206X termination mutation was identified in the hepatic nuclear factor 1α (HNF1α) gene. The mutation was identified in the proband and 8 of the 14 family members tested. An MMTT stimulus (±2.5 and 5 mg glibenclamide) produced a similar glucose profile and C-peptide graph in both the obese proband and her nonobese mother, showing no effect of the glibenclamide. No evidence of liver adenomas was found in the abdominal ultrasonography. Conclusions: We described a novel c.618G>A, p.W206X mutation in HNF1α associated with MODY 3 but not with hepatocellular adenoma. In contradistinction to most MODY 3 mutations, treatment with sulphonylurea was found to be a clinically ineffective alternative to insulin therapy.

Original languageEnglish
Pages (from-to)280-284
Number of pages5
JournalHormone Research in Paediatrics
Volume81
Issue number4
DOIs
StatePublished - May 2014

Keywords

  • Hepatic nuclear factor 1α
  • Hepatocellular adenoma
  • Maturity-onset diabetes of the young
  • Monogenic diabetes
  • Sulphonylurea

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