A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2
The article presents a variant of maturity onset diabetes of the young type 2, caused by a rare mutation in the GCK gene. Maturity onset diabetes of the young (MODY) is a hereditary form of diabetes with an autosomal dominant type of inheritance, an onset at a young age, and a primary defect in panc...
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| Format: | Article |
| Language: | English |
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2020-05-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/2458 |
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| author | D. E. Ivanoshchuk E. V. Shakhtshneider A. K. Ovsyannikova S. V. Mikhailova O. D. Rymar V. I. Oblaukhova A. A. Yurchenko M. I. Voevoda |
| author_facet | D. E. Ivanoshchuk E. V. Shakhtshneider A. K. Ovsyannikova S. V. Mikhailova O. D. Rymar V. I. Oblaukhova A. A. Yurchenko M. I. Voevoda |
| author_sort | D. E. Ivanoshchuk |
| collection | DOAJ |
| description | The article presents a variant of maturity onset diabetes of the young type 2, caused by a rare mutation in the GCK gene. Maturity onset diabetes of the young (MODY) is a hereditary form of diabetes with an autosomal dominant type of inheritance, an onset at a young age, and a primary defect in pancreatic β-cell function. This type of diabetes is different from classical types of diabetes mellitus (DM1 and DM2) in its clinical course, treatment strategies, and prognosis. Clinical manifestations of MODY are heterogeneous and may vary even among members of the same family, i. e., carriers of identical mutations. This phenotypic variation is due to the interaction of mutations with different genetic backgrounds and the influence of environmental factors (e. g., lifestyle). Using next-generation sequencing technology, the c.580–1G>A substitution (IVS5 –1G>A, rs1554335421) located in an acceptor splice site of intron 5 of the GCK gene was found in a proband. The identified variant cosegregated with a pathological phenotype in the examined family members. The GCK gene encodes glucokinase (hexokinase 4), which catalyzes the first step in a large number of glucose metabolic pathways such as glycolysis. Mutations in this gene are the cause of MODY2. The illness is characterized by an insignificant increase in the fasting glucose level, is a well-controlled disease without medication, and has a low prevalence of micro- and macrovascular complications of diabetes. The presented case of MODY2 reveals the clinical significance of a mutation in the splice site of the GCK gene. When nonclassical diabetes mellitus is being diagnosed in young people and pregnant women, genetic testing is needed to verify the diagnosis and to select the optimal treatment method. |
| format | Article |
| id | doaj-art-c6bcdca5afb44ae4a4ad31dd0a5f3693 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-c6bcdca5afb44ae4a4ad31dd0a5f36932025-02-01T09:58:08ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592020-05-0124329930510.18699/VJ20.41-o1015A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2D. E. Ivanoshchuk0E. V. Shakhtshneider1A. K. Ovsyannikova2S. V. Mikhailova3O. D. Rymar4V. I. Oblaukhova5A. A. Yurchenko6M. I. Voevoda7Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences; Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesResearch Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences; Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesResearch Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesResearch Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesResearch Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences; Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesThe article presents a variant of maturity onset diabetes of the young type 2, caused by a rare mutation in the GCK gene. Maturity onset diabetes of the young (MODY) is a hereditary form of diabetes with an autosomal dominant type of inheritance, an onset at a young age, and a primary defect in pancreatic β-cell function. This type of diabetes is different from classical types of diabetes mellitus (DM1 and DM2) in its clinical course, treatment strategies, and prognosis. Clinical manifestations of MODY are heterogeneous and may vary even among members of the same family, i. e., carriers of identical mutations. This phenotypic variation is due to the interaction of mutations with different genetic backgrounds and the influence of environmental factors (e. g., lifestyle). Using next-generation sequencing technology, the c.580–1G>A substitution (IVS5 –1G>A, rs1554335421) located in an acceptor splice site of intron 5 of the GCK gene was found in a proband. The identified variant cosegregated with a pathological phenotype in the examined family members. The GCK gene encodes glucokinase (hexokinase 4), which catalyzes the first step in a large number of glucose metabolic pathways such as glycolysis. Mutations in this gene are the cause of MODY2. The illness is characterized by an insignificant increase in the fasting glucose level, is a well-controlled disease without medication, and has a low prevalence of micro- and macrovascular complications of diabetes. The presented case of MODY2 reveals the clinical significance of a mutation in the splice site of the GCK gene. When nonclassical diabetes mellitus is being diagnosed in young people and pregnant women, genetic testing is needed to verify the diagnosis and to select the optimal treatment method.https://vavilov.elpub.ru/jour/article/view/2458humanmaturity onset diabetes of the youngmody2glucokinase genenext-generation sequencinggenetic analysisbioinformatics |
| spellingShingle | D. E. Ivanoshchuk E. V. Shakhtshneider A. K. Ovsyannikova S. V. Mikhailova O. D. Rymar V. I. Oblaukhova A. A. Yurchenko M. I. Voevoda A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2 Вавиловский журнал генетики и селекции human maturity onset diabetes of the young mody2 glucokinase gene next-generation sequencing genetic analysis bioinformatics |
| title | A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2 |
| title_full | A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2 |
| title_fullStr | A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2 |
| title_full_unstemmed | A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2 |
| title_short | A rare splice site mutation in the gene encoding glucokinase/hexokinase 4 in a patient with MODY type 2 |
| title_sort | rare splice site mutation in the gene encoding glucokinase hexokinase 4 in a patient with mody type 2 |
| topic | human maturity onset diabetes of the young mody2 glucokinase gene next-generation sequencing genetic analysis bioinformatics |
| url | https://vavilov.elpub.ru/jour/article/view/2458 |
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