Ivanoshchuk D E, Shakhtshneider E V, Ovsyannikova A K, Mikhailova S V, Rymar O D, Oblaukhova V I, Yurchenko A A, Voevoda M I
Research Institute of Internal and Preventive Medicine - Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Research Institute of Internal and Preventive Medicine - Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2020 May;24(3):299-305. doi: 10.18699/VJ20.41-o.
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. Key words: human; maturity onset diabetes of the young; MODY2; glucokinase gene; next-generation sequencing; genetic analysis; bioinformatics.
本文介绍了一种青年发病的成年型糖尿病2型变体，由GCK基因的罕见突变引起。青年发病的成年型糖尿病（MODY）是一种遗传性糖尿病，具有常染色体显性遗传类型，发病年龄较轻，胰腺β细胞功能存在原发性缺陷。这种糖尿病在临床病程、治疗策略和预后方面与经典类型的糖尿病（DM1和DM2）不同。MODY的临床表现具有异质性，即使在同一家族成员（即相同突变携带者）中也可能有所不同。这种表型变异是由于突变与不同遗传背景的相互作用以及环境因素（如生活方式）的影响。使用下一代测序技术，在先证者中发现了位于GCK基因第5内含子受体剪接位点的c.580-1G>A替换（IVS5 -1G>A，rs1554335421）。所鉴定的变体与受检家庭成员的病理表型共分离。GCK基因编码葡萄糖激酶（己糖激酶4），它催化大量葡萄糖代谢途径（如糖酵解）的第一步。该基因的突变是MODY2的病因。该疾病的特征是空腹血糖水平轻度升高，无需药物治疗即可得到良好控制，糖尿病微血管和大血管并发症的患病率较低。所呈现的MODY2病例揭示了GCK基因剪接位点突变的临床意义。在诊断年轻人和孕妇的非经典糖尿病时，需要进行基因检测以核实诊断并选择最佳治疗方法。关键词：人类；青年发病的成年型糖尿病；MODY2；葡萄糖激酶基因；下一代测序；遗传分析；生物信息学
