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

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Abstract

Aims

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).

Methods

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.

Results

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.

Conclusions

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

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Acknowledgements

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

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Authors and Affiliations

  1. Department and Laboratory of Inherited Endocrine Disorders, Endocrinology Research Centre, Ulitsa Dmitriya Ulianova, 11, 117036, Moscow, Russian Federation

    Natalia Zubkova, Vasily Petrov, Evgeny Vasilyev, Ekaterina Sorkina, Nina Makretskaya & Anatoly Tiulpakov

  2. Moscow Regional Research Institute of Obstetrics and Gynecology, Moscow, Russian Federation

    Fatima Burumkulova, Margarita Plechanova, Vasily Petrukhin, Anton Panov & Victoria Ulyatovskaya

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  1. Natalia Zubkova
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Corresponding author

Correspondence to Natalia Zubkova.

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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).

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Written informed consent was obtained from all study participants.

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Zubkova, N., Burumkulova, F., Plechanova, M. et al. High frequency of pathogenic and rare sequence variants in diabetes-related genes among Russian patients with diabetes in pregnancy. Acta Diabetol 56, 413–420 (2019). https://doi.org/10.1007/s00592-018-01282-6

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  • DOI: https://doi.org/10.1007/s00592-018-01282-6

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