Monogenic Syndromes as a Cause of Adverse Drug Reactions in the Russian Population.

Adverse drug reactions (ADRs) remain a major public health issue, and genetic factors contribute importantly to interindividual variability in drug response. Pharmacogenetic testing helps reduce ADR risk by optimizing drug selection and dosage, particularly in monogenic disorders. Whole-exome sequencing of 6739 samples from the Russian population was performed on the DNBSEQ-G400 platform (MGI). Variants in 48 genes were examined, focusing on inherited arrhythmias, enzyme deficiencies (Glucose-6-Phosphate Dehydrogenase Deficiency [G6PDD], Porphyrias), Dravet Syndrome (DS) and Malignant Hyperthermia (MH). Variants reported as pathogenic (P), likely pathogenic (LP), or variants of uncertain significance (VUS) in ClinVar were manually re-evaluated using ACMG criteria. A total of 75 unique variants in 18 genes were observed in 119 individuals (1.77%), including 21 carriers and 13 women with a G6PD mutation. Of these, 44 variants were classified as P, 24 as LP, and 7 as VUS. Missense variants accounted for the largest proportion (73.33%). The most affected genes were KCNQ1 (24/119), which exhibited the highest number of unique variants (18), G6PD (20/119), SCN1A (15/119), and RYR1 (14/119). Regarding associated conditions, mutations linked to arrhythmias were found in 51 individuals, MH in 27, G6PDD in 20, DS in 15, and Porphyrias in 6. Integrating common and rare clinically actionable genetic variants with attention to penetrance and clinical validity may improve medication safety, reduce preventable ADRs, and enhance personalized pharmacotherapy.