The G319S variants of the HNF1A gene in a family with diabetes mellitus


DOI: https://dx.doi.org/10.18565/therapy.2021.9.148-154

Ivanoshchuk D.E., Mikhailova S.V., Ovsyannikova A.K., Shakhtshneider E.V., Druk I.V., Rymar O.D., Voevoda M.I.

1) Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk; 2) Research Institute of Therapy and Preventive Medicine – a branch of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk; 3) Omsk State Medical University of the Ministry of Healthcare of Russia; 4) Federal Research Center for Fundamental and Translational Medicine, Novosibirsk
Abstract. In the process of differential diagnosis of the diabetes mellitus (DM) type, the greatest difficulty is presented by patients with the onset of the disease at a young age, since in this age group type 1 diabetes, type 2 diabetes and monogenic forms of diabetes (including MODY diabetes) could be manifesting.
The aim of the study is to show the possibilities of molecular genetic research for MODY-HNF1A and type 2 diabetes mellitus with early onset on the example of a clinical case of diabetes in a proband with a burdened family anamnesis.
Material and methods. The proband and the mother of the proband underwent targeted DNA sequencing using the Illumina MiSeq NGS System (Illumina Inc., San Diego, CA, USA). The target panel included the coding regions and adjacent splicing sites of MODY-associated genes: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1.
Results. The previously described heterozygous variant rs137853240 was found, which is located at the 3 ‘end of exon 4 of the HNF1A gene, near the highly conserved splice donor site and leads to a change in the set of transcripts encoded by this gene. Previously, it was shown that this substitution is associated with early onset of type 2 diabetes mellitus in an isolated population of the indigenous communities of Canada (the Oji-Kree population). Therefore, we estimated its prevalence in samples of the Koryaks, Chukchi, and Eskimos of Canada. Additionally, we analyzed population samples of the population of Western Siberia and patients with type 2 diabetes. In all studied samples, carriers of c.955G> A, p.Gly319Ser (rs137853240) were not found. Taking into account the described phenotypic features of individuals carrying the Gly319Ser variant, we assume that this variant is associated with the development of MODY.
Conclusion. The presented clinical case demonstrates the possibilities of molecular genetic study of monogenic forms of diabetes mellitus, in particular, associated with HNF1A gene analysis. A personalized approach to diagnosis and treatment is especially important in identifying a nonclassical course of diabetes in young people.
Keywords: HNF1A gene, new generation sequencing, MODY-diabetes, human genetics, rs137853240, populations, type 2 diabetes mellitus
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About the Autors

Dinara E. Ivanoshchuk, junior researcher of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, researcher of the Research Institute of Therapy and Preventive Medicine – a branch of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences. Address: 630090, Novosibirsk, 10 Akademika Lavrentieva Avenue. Tel.: +7 (961) 874-12-16. E-mail: dinara2084@mail.ru. ORCID: 0000-0002-0403-545X
Svetlana V. Mikhailova, PhD, researcher of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences. Address: Novosibirsk, 10 Prospect Akademika Lavrentieva Avenue. Tel.: +7 (913) 910-24-63. E-mail: mikhail@bionet.nsc.ru. ORCID: 0000-0002-0897-5473
Alla K. Ovsyannikova, PhD, senior researcher of the Research Institute of Therapy and Preventive Medicine – a branch of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences. Address: 630089, Novosibirsk, 175/1 Borisa Bogatkova Str. Tel.: +7 (383) 373-09-89. E-mail: aknikolaeva@bk.ru. ORCID: 0000-0002-9669-745X
Elena V. Shakhtshneider, PhD, deputy head of scientific work, Research Institute of Therapy and Preventive Medicine – a branch of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, head of the sector for the study of monogenic forms of common human diseases, Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences. Address: 630089, Novosibirsk, 175/1 Borisa Bogatkova Str. Tel..: +7 (383) 373-09-82. E-mail: 2117409@mail.ru. ORCID: 0000-0001-6108-1025
Inna V. Druk, MD, associate professor, head of the Department of internal diseases and family medicine, Omsk State Medical University of the Ministry of Healthcare of Russia. Address: 644033, Omsk, 127/1 Krasny Put` Str. Tel.: +7 (381) 249-20-85. E-mail: osma-genpract@yandex.ru. ORCID: 0000-0001-8317-7765
Oksana D. Rymar, MD, head of the laboratory of clinical-population and preventive studies of therapeutic and endocrine diseases, Research Institute of Therapy and Preventive Medicine – a branch of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences. Address: 630089, Novosibirsk, 175/1 Borisa Bogatkova Str. Tel.: +7 (383) 373-09-89. E-mail: orymar23@gmail.com. ORCID: 0000-0003-4095-0169
Mikhail I. Voevoda, MD, professor, academician of RAS, Director of Federal Research Center for Fundamental and Translational Medicine. Address: 630117, Novosibirsk, 2 Timakova Str. E-mail: mvoevoda@ya.ru. ORCID: 0000-0003-4716-876X


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