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A rare splice site mutation (IVS5; -1G>A) of the GCK gene



Maturity onset diabetes of the young (MODY) is a hereditary form of diabetes with an autosomal dominant type of inheritance, onset at a young age, and a primary defect in pancreatic β-cells function. The article presents a variant of maturity onset diabetes of the young type 2, caused by a rare mutation in the GCK gene encoding glucokinase/hexokinase 4. Identified substitution c.580-1G>A [IVS5 (-1G>A)] is located in an acceptor splice site of intron 5 of GCK. A heterozygous mutation in the GCK gene was found by next-generation sequencing. IVS5 (-1G>A) of GCK cosegregates 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 the GCK gene are the cause of MODY2. The disease is characterized by an insignificant increase in the fasting glucose level, well-controlled disease without medication, and low prevalence of micro- and macrovascular complications of diabetes. When nonclassical diabetes mellitus is being diagnosed in young people, genetic testing is needed to verify the diagnosis.

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