Molecular genetic testing is highly recommended for patients suspected of monogenic diabetes as it allows tailoring treatments to specific etiological mechanisms. Using WES, we studied the frequency and the spectrum of genetic variants causative of monogenic diabetes in a cohort of Russian children with non-type 1 diabetes mellitus.
A total of 60 unrelated patients with diabetes and impaired glucose tolerance (pre-diabetes) were prospectively included in the study (Russian ethnicity and resided in Northwest Russia). Genetic variants were screened by WES in a panel of 35 genes causative of maturity onset diabetes of the young (MODY) and transient or permanent neonatal diabetes.
A total of 38 genetic variants were detected in 33 out of 60 patients (55%). Most of patients (27/33, 81.8%) had variants in MODY-related genes: GCK (n=19), HNF1A (n=2), PAX4 (n=1), ABCC8 (n=1), KCNJ11 (n=1), GCK+HNF1A (n=1), GCK+BLK (n=1), and GCK+BLK+WFS1 (n=1). In 6 patients (6/33, 18.2%), variants in MODY-unrelated genes were found: GATA6 (n=1), WFS1 (n=3), EIF2AK3 (n=1), and SLC19A2 (n=1). Fifteen out of 38 variants were novel ones: in GCK, HNF1A, BLK, WFS1, EIF2AK3, and SLC19A2.
Our data show a high frequency and a wide spectrum of genetic variants causative of MODY in Russian children. The prevalence of GCK variants suggests that diagnostics of monogenic diabetes in Russian children may start with testing for MODY2. However, the remaining variants are present at low frequencies in 9 different genes, altogether amounting to approximately half of the cases and thus highlighting the efficiency of using WES in non-GCK-MODY cases.