High frequency of pathogenic and rare sequence variants in diabetes-related genes among Russian patients with diabetes in pregnancy

  • Natalia ZubkovaEmail author
  • Fatima Burumkulova
  • Margarita Plechanova
  • Vasily Petrukhin
  • Vasily Petrov
  • Evgeny Vasilyev
  • Anton Panov
  • Ekaterina Sorkina
  • Victoria Ulyatovskaya
  • Nina Makretskaya
  • Anatoly Tiulpakov
Original Article
Part of the following topical collections:
  1. Pregnancy and diabetes



Diabetes in pregnancy may be associated with monogenic defects of beta-cell function, frequency of which depends on ethnicity, clinical criteria for selection of patients as well as methods used for genetic analysis. The aim was to evaluate the contribution and molecular spectrum of mutations among genes associated with monogenic diabetes in non-obese Russian patients with diabetes in pregnancy using the next-generation sequencing (NGS).


188 non-obese pregnant women with diabetes during pregnancy were included in the study; among them 57 subjects (30.3%) met the American Diabetes Association (ADA) criteria of preexisting pregestational diabetes (pre-GDM), whereas 131 women (69.7%) fulfilled criteria of gestational diabetes mellitus (GDM). A custom NGS panel targeting 28 diabetes causative genes was used for sequencing. The sequence variants were rated according to the American College of Medical Genetics and Genomics (ACMG) guidelines.


In total, 23 pathogenic, 18 likely pathogenic and 16 variants of uncertain significance were identified in 59/188 patients (31.4%). The majority of variants (38/59) were found in GCK gene. No significant differences in the number of variants among the two study groups (pre-GDM and GDM) were observed.


The study suggests that frequency of monogenic variants of diabetes might be underestimated, which warrants a broader use of genetic testing, especially in pregnancy.


Non-obese pregnant women Diabetes in pregnancy Next-generation sequencing Monogenic forms of diabetes 



This study was supported by the Grant 16-15-10408 of the Russian Science Foundation.

Compliance with ethical standards

Conflict of interest

The authors declare they have no conflict of interest.

Ethical approval

This study was approved by the local ethics committee of the Moscow Regional Research Institute of Obstetrics and Gynecology (Protocol no. 88 dated 30.06.2016).

Informed consent

Written informed consent was obtained from all study participants.


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  • Natalia Zubkova
    • 1
    Email author
  • Fatima Burumkulova
    • 2
  • Margarita Plechanova
    • 2
  • Vasily Petrukhin
    • 2
  • Vasily Petrov
    • 1
  • Evgeny Vasilyev
    • 1
  • Anton Panov
    • 2
  • Ekaterina Sorkina
    • 1
  • Victoria Ulyatovskaya
    • 2
  • Nina Makretskaya
    • 1
  • Anatoly Tiulpakov
    • 1
  1. 1.Department and Laboratory of Inherited Endocrine DisordersEndocrinology Research CentreMoscowRussian Federation
  2. 2.Moscow Regional Research Institute of Obstetrics and GynecologyMoscowRussian Federation

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