Breaking a single hydrogen bond in the mitochondrial tRNA -PheRS complex leads to phenotypic pleiotropy of human disease.

Various pathogenic variants in both mitochondrial tRNA and Phenylalanyl-tRNA synthetase mitochondrial protein coding gene (FARS2) gene encoding for the human mitochondrial PheRS have been identified and associated with neurological and/or muscle-related pathologies. An important Guanine-34 (G34)A anticodon mutation associated with myoclonic epilepsy with ragged red fibers (MERRF) syndrome has been reported in hmit-tRNA . The majority of G34 contacts in available aaRSs-tRNAs complexes specifically use that base as an important tRNA identity element.

Kinetic and structural changes in HsmtPheRS, induced by pathogenic mutations in human FARS2.

Mutations in the mitochondrial aminoacyl-tRNA synthetases (mtaaRSs) can cause profound clinical presentations, and have manifested as diseases with very selective tissue specificity. To date most of the mtaaRS mutations could be phenotypically recognized, such that clinicians could identify the affected mtaaRS from the symptoms alone. Among the recently reported pathogenic variants are point mutations in FARS2 gene, encoding the human mitochondrial PheRS.

Chimeric human mitochondrial PheRS exhibits editing activity to discriminate nonprotein amino acids.

Mitochondria are considered as the primary source of reactive oxygen species (ROS) in nearly all eukaryotic cells during respiration. The harmful effects of these compounds range from direct neurotoxicity to incorporation into proteins producing aberrant molecules with multiple physiological problems. Phenylalanine exposure to ROS produces multiple oxidized isomers: tyrosine, Levodopa, ortho-Tyr, meta-Tyr (m-Tyr), and so on.

[Two clinical cases of antiphospholipid syndrome].

Because of importance of early diagnosis of antiphospholypid syndrome (APS) we present two case histories from clinical practice of Scientific-Practical Center of Rheumatology. The first clinical case (male, born in 1961, diagnosed with systemic lupus erythematosus and secondary APS) shows that verification of diagnosis in men is much harder than in women. The patient was diagnosed with secondary APS only 8 years after the onset of the disease.

[Cytokines and smoking in the cases of reactive arthritis during urogenital chlamydiosis].

The aim of the work was the determination of blood serum cytokines level and identification of possible association of the latter with smoking in the case of reactive arthritis (ReA) developed on the background of urogenital chlamydiosis. 74 patients with ReA were tested. 19 patients had acute ReA (disease duration not exceeding 6 months from manifestation of chlamydiosis) and 55 - chronic ReA (disease duration exceeding 6 months from manifestation of chlamydiosis).