Coinheritance of HNF1A and glucokinase variants in maturity-onset diabetes of the young

Abstract

early-onset diabetes with dominant inheritance of beta-cell dysfunction. There are few reports of the coinheritance of glucokinase (GCK) and hepatocyte nuclear factor 1 alpha gene (HNF1A) variants underlying MODY in patients. Herein, we describe a case involving combinations of monoallelic GCK and HNF1A variants associated with MODY. A 10-year-old Japanese girl with a three-generation family history of diabetes without obesity showed high levels of urinary glucose during a school screening test. Her glucose metabolism profile revealed 124 mg/dL of fasting glucose, 6.9% glycated hemoglobin (HbA1c), and 2.78 ng/mL of C-peptide immunoreactivity levels. In a 75-g oral glucose tolerance test, her base glucose, peak glucose, insulin resistance, and homeostasis model assessment of beta cell function levels were 124 mg/dL, 210 mg/dL (120 min), 1.71, and 33%, respectively. Based on the clinical phenotype of GCK-MODY, alimentary and exercise therapy without oral hypoglycemic agents were used to maintain her fasting glucose and HbA1c levels. We explored the coinheritance of MODY with GCK and HNF1A variants in this and past cases and found that careful clinical follow-up is required to firmly establish phenotypic features. Moreover, the accumulation of data on genetically confirmed MODY associated with the coinheritance of GCK and HNF1A variants will be useful for understanding genotype–phenotype correlations.