Open Access

Whole‑exome sequencing in Russian children with non‑type 1 diabetes mellitus reveals a wide spectrum of genetic variants in MODY‑related and unrelated genes

  • Authors:
    • Oleg S. Glotov
    • Elena A. Serebryakova
    • Mariia E. Turkunova
    • Olga A. Efimova
    • Andrey S. Glotov
    • Yury A. Barbitoff
    • Yulia A. Nasykhova
    • Alexander V. Predeus
    • Dmitrii E. Polev
    • Mikhail A. Fedyakov
    • Irina V. Polyakova
    • Tatyana E. Ivashchenko
    • Natalia Y. Shved
    • Elena S. Shabanova
    • Alena V. Tiselko
    • Olga V. Romanova
    • Andrey M. Sarana
    • Anna A. Pendina
    • Sergey G. Scherbak
    • Ekaterina V. Musina
    • Anastasiia V. Petrovskaia‑Kaminskaia
    • Liubov R. Lonishin
    • Liliya V. Ditkovskaya
    • Liudmila А. Zhelenina
    • Ludmila V. Tyrtova
    • Olga S. Berseneva
    • Rostislav K. Skitchenko
    • Evgenii N. Suspitsin
    • Elena B. Bashnina
    • Vladislav S. Baranov
  • View Affiliations

  • Published online on: October 16, 2019     https://doi.org/10.3892/mmr.2019.10751
  • Pages: 4905-4914
  • Copyright: © Glotov et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study reports on the frequency and the spectrum of genetic variants causative of monogenic diabetes in Russian children with non‑type 1 diabetes mellitus. The present study included 60 unrelated Russian children with non‑type 1 diabetes mellitus diagnosed before the age of 18 years. Genetic variants were screened 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.
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December 2019
Volume 20 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Glotov, O.S., Serebryakova, E.A., Turkunova, M.E., Efimova, O.A., Glotov, A.S., Barbitoff, Y.A. ... Baranov, V.S. (2019). Whole‑exome sequencing in Russian children with non‑type 1 diabetes mellitus reveals a wide spectrum of genetic variants in MODY‑related and unrelated genes. Molecular Medicine Reports, 20, 4905-4914. https://doi.org/10.3892/mmr.2019.10751
MLA
Glotov, O. S., Serebryakova, E. A., Turkunova, M. E., Efimova, O. A., Glotov, A. S., Barbitoff, Y. A., Nasykhova, Y. A., Predeus, A. V., Polev, D. E., Fedyakov, M. A., Polyakova, I. V., Ivashchenko, T. E., Shved, N. Y., Shabanova, E. S., Tiselko, A. V., Romanova, O. V., Sarana, A. M., Pendina, A. A., Scherbak, S. G., Musina, E. V., Petrovskaia‑Kaminskaia, A. V., Lonishin, L. R., Ditkovskaya, L. V., Zhelenina, L. А., Tyrtova, L. V., Berseneva, O. S., Skitchenko, R. K., Suspitsin, E. N., Bashnina, E. B., Baranov, V. S."Whole‑exome sequencing in Russian children with non‑type 1 diabetes mellitus reveals a wide spectrum of genetic variants in MODY‑related and unrelated genes". Molecular Medicine Reports 20.6 (2019): 4905-4914.
Chicago
Glotov, O. S., Serebryakova, E. A., Turkunova, M. E., Efimova, O. A., Glotov, A. S., Barbitoff, Y. A., Nasykhova, Y. A., Predeus, A. V., Polev, D. E., Fedyakov, M. A., Polyakova, I. V., Ivashchenko, T. E., Shved, N. Y., Shabanova, E. S., Tiselko, A. V., Romanova, O. V., Sarana, A. M., Pendina, A. A., Scherbak, S. G., Musina, E. V., Petrovskaia‑Kaminskaia, A. V., Lonishin, L. R., Ditkovskaya, L. V., Zhelenina, L. А., Tyrtova, L. V., Berseneva, O. S., Skitchenko, R. K., Suspitsin, E. N., Bashnina, E. B., Baranov, V. S."Whole‑exome sequencing in Russian children with non‑type 1 diabetes mellitus reveals a wide spectrum of genetic variants in MODY‑related and unrelated genes". Molecular Medicine Reports 20, no. 6 (2019): 4905-4914. https://doi.org/10.3892/mmr.2019.10751