Genotype-based personalized correction of glycemic control in patients with MODY due to mutations in GCK, HNF1A AND HNF4A genes

Aims. To demonstrate the principles of personalized treatment of diabetes for example the most common MODY subtypes (1-3) identified by NGS

Methods. We study 312 patients aged from 3 months to 25 years (162 boy/150 girls) with suspected MODY. A targeted next-generation sequencing approach (IonTorrent platform) was used for sequencing of monogenic form of diabetes mellitus candidate 28genes (13 MODY genes-candidates and other genes, associated with diabetes mellitus). Clinical and biochemicalphenotypes of the patients were compared with the type of mutations. Previously undescribed nonsynonymous mutations were considered as «probably pathogenic» with the minor allele frequency of <0.1% and «pathogenic» assessment in ANNOVAR database.

Results. We selected group of patients with mutations in the most common genes-candidates (GCK; HNF1A; HNF4A):99GCK gene mutations detectedin the 129 probands (61,1%) and 77 relatives, in HNF1A – 20 mutations in the 19 probands(9,0%) and 14 relatives, in HNF4A – 8 mutations in 9the probands (4,3%) and 3 relatives. The current therapy wasmodificated account the genotype and have been evaluated its effectiveness.

Conclusion. Molecular genetic confirmation of the monogenic nature of metabolic carbohydratedisorders is the basis of personalized therapy of diabetes.

MODY, NGS, GCK, HNF1A, HNF4A, personalized therapy

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