NGS Analysis Revealed Digenic Heterozygous GCK and HNF1A Variants in a Child with Mild Hyperglycemia: A Case Report.

ABSTRACT

Monogenic diabetes (MD) represents a heterogeneous group of disorders whose most frequent form is maturity-onset diabetes of the young (MODY). MD is predominantly caused by a mutation in a single gene. We report a case of a female patient with suspected MD and a positive family history for diabetes and obesity. In this patient, two gene variants have been identified by next-generation sequencing (NGS) one in the Glucokinase (GCK) gene reported in the Human Gene Mutation Database (HGMD) and in the literature associated with GCK/MODY, and the other in the hepatocyte nuclear factor 1A (HNF1A) gene not previously described. The GCK variant was also identified in the hyperglycemic father, whereas the HNF1A variant was present in the mother. This new case of digenic GCK/HNF1A variants identified in a hyperglycemic subject, evidences the importance of NGS analysis in patients with suspected MD. In fact, this methodology will allow us to both increase the number of diagnoses and to identify mutations in more than one gene, with a better understanding of the genetic cause, and the clinical course, of the disease.