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

• Published in: Diagnostics (Basel) Vol. 11; no. 7; p. 1164
• Main Authors: Iafusco, Fernanda, Maione, Giovanna, Mazzaccara, Cristina, Di Candia, Francesca, Mozzillo, Enza, Franzese, Adriana, Tinto, Nadia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-06-2021; MDPI
• Subjects: Age; Case Report; Case reports; Cholesterol; Diabetes; digenic variants; Families & family life; Family medical history; Fasting; GCK/MODY; Genes; Genomics; Glucose; HNF1A/MODY; Hyperglycemia; Insulin resistance; Mutation; Patients; Pediatrics; Pregnancy; United States > US; Germany; hyperglycemia; digenic variants; HNF1A/MODY; GCK/MODY
• ISSN: 2075-4418; 2075-4418
• DOI: 10.3390/diagnostics11071164

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 (
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 (
) gene not previously described. The
variant was also identified in the hyperglycemic father, whereas the
variant was present in the mother. This new case of digenic
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.