A synonymous variant in GCK gene as a cause of gestational diabetes mellitus
Natalia A. Zubkova,
Petr M. Rubtsov,
Fatima F. Burumkulova,
Liudmila I. Ibragimova,
Nina A. Makretskaya,
Evgeny V. Vasilyev,
Vasily M. Petrov,
Anatoly N. Tiulpakov https://doi.org/10.14341/DM9938
Abstract
The diagnosis of MODY as a subtype of gestational diabetes mellitus (GDM) is important for an adequate management during pregnancy and the postnatal period. The present report describes a case of GDM caused by a synonymous с.666C>G р.V222V substitution in the GCK gene. The variant, which was initially ranked as ‘likely benign’, was later proven to be pathogenic by in vitro studies. The с.666C>G substitution led to the use of a new donor splice site and synthesis of the aberrant mRNA with deletion of 16 base pairs. The case illustrates that additional clinical and experimental data may be required for the correct interpretation of sequence variants pathogenicity.
About the Authors
Natalia A. Zubkova
Endocrinology Research Centre
Russian Federation
Russian Federation
MD, PhD, senior research associate
Petr M. Rubtsov
Engelhardt Institute of Molecular Biology Russian Academy of Sciences
Russian Federation
Russian Federation
PhD in Biology, leading research associate
Fatima F. Burumkulova
Moscow Regional Research Institute of Obstetrics and Gynecology
Russian Federation
Russian Federation
MD, PhD, leading research associate
Liudmila I. Ibragimova
Endocrinology Research Centre
Russian Federation
Russian Federation
MD, PhD, senior research associate
Nina A. Makretskaya
Endocrinology Research Centre
Russian Federation
Russian Federation
MD, research associate
Evgeny V. Vasilyev
Endocrinology Research Centre
Russian Federation
Russian Federation
PhD in Biology, senior research associate
Vasily M. Petrov
Endocrinology Research Centre
Russian Federation
Russian Federation
PhD in Chemistry, senior research associate
Anatoly N. Tiulpakov
Endocrinology Research Centre
Russian Federation
Russian Federation
MD, PhD
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Supplementary files
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1. Fig. 1. Daily monitoring of glycemia in patient L. before prescribing insulin therapy. | |
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2. Fig. 2. Daily monitoring of glycemia of the patient L. after the appointment of insulin therapy. | |
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3. Fig. 3. The family tree of the patient's family L .: SD - diabetes mellitus. | |
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4. Fig. 4. Chromatogram with the results of sequencing of splicing products obtained in vitro using the technology of "minigena" [5]. WT is a fragment of the wild-type transcript sequence; c663_678del - a fragment of a transcript with a deletion of 16 base pairs as a result of the synonymous variant c.666C> G. | |
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For citations:
Zubkova N.A., Rubtsov P.M., Burumkulova F.F., Ibragimova L.I., Makretskaya N.A., Vasilyev E.V., Petrov V.M., Tiulpakov A.N. A synonymous variant in GCK gene as a cause of gestational diabetes mellitus. Diabetes mellitus. 2019;22(2):165-169. (In Russ.) https://doi.org/10.14341/DM9938
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