Molecular changes in the Glucokinase gene (GCK) associated with the diagnosis of Maturity Onset Diabetes of the Young (MODY) in pregnant women and newborns

Abstract

Background: Diabetes Mellitus is the most common metabolic alteration in gestation. Monogenic diabetes or Maturity-Onset Diabetes of the Young (MODY) consists in a subtype caused by primary defect in insulin secretion determined by dominant autosomal inheritance. Objectives: To analyze molecular changes of the Glucokinase gene (GCK) in pregnant women with hyperglycemia during gestation and in their neonates. Case study and Methods: We collected 201 blood samples, 128 from pregnant patients diagnosed with hyperglycemia and 73 from umbilical cord blood from neonates of the respective patients. We performed DNA extraction and polymerase chain reaction (PCR) to identify molecular changes in the GCK gene. Results: In a total of 201 samples (128 from mothers and 73 from neonates), we found changes in 21 (10.6%), 12 maternal samples (6.0%) and 9 neonatal samples (4.5%). DNA sequencing identified two polymorphisms and one deleterious MODY GCK-diagnostic mutation. Conclusions: The prevalence of molecular changes of the Glucokinase gene (GCK) and the deleterious MODY GCK-diagnostic mutation were, respectively, 9.3% and 0.7% in women with hyperglycemia during gestation and 12.5% and 1.3% in their neonates. The deleterious MODY GCK mutation identified is associated reduction in GCK activity and hyperglycemia. In the others molecular changes identified despite not having clinical significance, it was not possible to exclude phenotypic change. Therefore, these changes may interfere with the management and clinical outcome of the patients.