A Family with a Novel Termination Mutation in Hepatic Nuclear Factor 1[alpha] in Maturity-Onset Diabetes of the Young Type 3 Which Is Unresponsive to Sulphonylurea Therapy

• Published in: Hormone research in paediatrics Vol. 81; no. 4; p. 280
• Main Authors: Demol, S, Lebenthal, Y, Bar-meisels, M, Phillip, M, Gat-yablonski, G, Gozlan, Y
• Format: Journal Article
• Language: English
• Published: Basel S. Karger AG 01.05.2014
• ISSN: 1663-2818; 1663-2826
• DOI: 10.1159/000356925

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. © 2014 S. Karger AG, Basel [PUBLICATION ABSTRACT]