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20.01.2019 | Original Article

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

verfasst von: Natalia Zubkova, Fatima Burumkulova, Margarita Plechanova, Vasily Petrukhin, Vasily Petrov, Evgeny Vasilyev, Anton Panov, Ekaterina Sorkina, Victoria Ulyatovskaya, Nina Makretskaya, Anatoly Tiulpakov

Erschienen in: Acta Diabetologica | Ausgabe 4/2019

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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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Titel: High frequency of pathogenic and rare sequence variants in diabetes-related genes among Russian patients with diabetes in pregnancy
verfasst von: Natalia Zubkova
Fatima Burumkulova
Margarita Plechanova
Vasily Petrukhin
Vasily Petrov
Evgeny Vasilyev
Anton Panov
Ekaterina Sorkina
Victoria Ulyatovskaya
Nina Makretskaya
Anatoly Tiulpakov
Publikationsdatum: 20.01.2019
Verlag: Springer Milan
Erschienen in: Acta Diabetologica / Ausgabe 4/2019
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-018-01282-6

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

Abstract

Aims

Methods

Results

Conclusions

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Abstract

Aims

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Results

Conclusions

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