CLINICAL APPLICATION OF MASSIVE PARALLEL SEQUENCING IN MOLECULAR DIAGNOSTICS OF HEREDITARY DISEASES OF GLYCOGEN ACCUMULATION IN THE CHILDREN POPULATION OF THE RUSSIAN FEDERATION

Abstract

There has been developed and validated the technology for massive parallel sequencing for the purpose of molecular genetic diagnosis of hereditary glycogen storage diseases. Among 96 patients aged of from 15 months up to 18 years, the diagnosis was verified in 89 (92.6%) children. Glycogen storage disease (GSD) type IX appeared to be the most frequent form of glycogenosis in children, diagnosed in 29.3% of cases, GSD type IV, verified in 1.1% of cases, was a rare form of glycogenesis. In 39 (43.8%) out of 89 genetically confirmed children, there were revealed 35 (44.3%) of the previously undescribed mutations from 79 pathogenic variants found in 9 (45%) of different genes of 20 examined cases, indicating to a significant heterogeneity of genetic factors of the development of GSD in the Russian population. Mutations c.247C>T of the G6PC gene, c.1042_1043del of the SLC37A4 gene, c.3980G>A and c.1423+1G>A of the AGL gene, c.-32-13T>G of the GAA gene, and c.884G>A of the PHKA2 gene were been established to be characteristic for the Russian population of GSD children. There was shown the high sensitivity and specificity of the massive parallel sequencing for the search for single nucleotide substitutions in coding and adjacent intron regions, as well as small deletions and duplications of genes, mutations in which lead to the development of GSD. Massive parallel sequencing is necessary for the rapid diagnosis of GSD, timely appointment of the adequate treatment, prevention of complications, which will improve the quality of the life of GSD patients.