Application of NGS to improve the effectiveness of molecular genetic diagnostics of monogenic forms of diabetes in children
https://doi.org/10.25557/2073-7998.2020.05.86-88
Abstract
The present study included 60 unrelated Russian children with non-type 1 diabetes mellitus diagnosed before the age of 18 years. Genetic variants were analyzed using whole-exome sequencing (WES) in a panel of 35 genes causative of maturity onset diabetes of the young (MODY) and transient or permanent neonatal diabetes. Verification of the WES results was performed using PCR-direct sequencing. A total of 38 genetic variants were identified in 33 out of 60 patients (55%). The majority 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). A total of 6 patients (6/33, 18.2%) had variants in MODY-unrelated genes: GATA6 (n=1), WFS1 (n=3), EIF2AK3 (n=1) and SLC19A2 (n=1). A total of 15 out of 38 variants were novel, including GCK, HNF1A, BLK, WFS1, EIF2AK3 and SLC19A2. To summarize, the present study demonstrates a high frequency and a wide spectrum of genetic variants causative of monogenic diabetes in Russian children with non-type 1 diabetes mellitus. The spectrum includes previously known and novel variants in MODY-related and unrelated genes, with multiple variants in a number of patients. The prevalence of GCK variants indicates that diagnostics of monogenic diabetes in Russian children may begin with testing for MODY2. However, the remaining variants are present at low frequencies in 9 different genes, altogether amounting to ~50% of the cases and highlighting the efficiency of using WES in non-GCK-MODY cases.
About the Authors
O. S. Glotov
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology
Russian Federation
Russian Federation
E. A. Serebryakova
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology
Russian Federation
Russian Federation
M. E. Turkunova
St. Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
E. B. Bashnina
North-Western State Medical University named after I.I. Mechnikov
Russian Federation
Russian Federation
A. S. Glotov
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology
Russian Federation
Russian Federation
Yu. A. Barbitoff
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology
Russian Federation
Russian Federation
D. E. Polev
LLC «Serbalab»
Russian Federation
Russian Federation
T. E. Ivashchenko
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology
Russian Federation
Russian Federation
M. A. Fedyakov
City hospital №40
Russian Federation
Russian Federation
A. M. Sarana
Sankt-Saint Petersburg State University
Russian Federation
Russian Federation
S. G. Scherbak
City hospital №40
Russian Federation
Russian Federation
V. S. Baranov
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology
Russian Federation
Russian Federation
Review
For citations:
Glotov O.S., Serebryakova E.A., Turkunova M.E., Bashnina E.B., Glotov A.S., Barbitoff Yu.A., Polev D.E., Ivashchenko T.E., Fedyakov M.A., Sarana A.M., Scherbak S.G., Baranov V.S. Application of NGS to improve the effectiveness of molecular genetic diagnostics of monogenic forms of diabetes in children. Medical Genetics. 2020;19(5):86-88. (In Russ.) https://doi.org/10.25557/2073-7998.2020.05.86-88
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