title: 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.
abstract: BACKGROUND
  Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus.
  
  
  OBJECTIVE
  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.
authors.affiliation: The Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Demol
authors.forename: Y
authors.initials: Y
authors.lastname: Lebenthal
authors.forename: M
authors.initials: M
authors.lastname: Bar-Meisels
authors.forename: M
authors.initials: M
authors.lastname: Phillip
authors.forename: G
authors.initials: G
authors.lastname: Gat-Yablonski
authors.forename: Y
authors.initials: Y
authors.lastname: Gozlan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds