ABSTRACT
The review is devoted to the analysis of the current state of pharmacogenetic research and their use in psychiatric practice. The main genes responsible for the pharmacodynamics and pharmacokinetics of drugs used in psychiatry are listed. Foreign pharmacogenetic clinical recommendations and progress on their implementation in medical practice in various countries of Europe and the USA are analyzed. The need to create Russian clinical guidelines on pharmacogenomics to improve the effectiveness of patient care and to implement a personalized approach to therapy is discussed.
Subject(s)
Neurology , Pharmacogenetics , Psychiatry , Europe , Humans , Russia , United StatesABSTRACT
BACKGROUND: Cutis laxa (CL) is a rare connective tissue disorder characterized by loose, redundant, inelastic and wrinkled skin. Patients develop a prematurely aged appearance. Inheritance can be autosomal dominant or autosomal recessive. The X-linked form is now classified in the group of copper transport diseases. Autosomal dominant CL is characterized by wrinkled, redundant and sagging, inelastic skin and in some cases is associated with internal organ involvement. CASE PRESENTATION: We report a familial case of autosomal dominant CL, which includes a 33-year-old woman and her 11-year-old son with dry, thin and wrinkled skin that appeared prematurely aged. No serious involvement of internal organs was found. In both patients, we identified novel heterozygous mutation c.2323delG (p.Ala775fs) in exon 34 of elastin transcript NM_001278939.1. Similar frameshift mutations in the last exons of elastin gene were previously reported in patients with autosomal dominant CL. CONCLUSIONS: Our results show a novel frameshift mutation that was found in patients with cutis laxa. Exome sequencing is effective and useful technology for properly diagnosis of diseases with similar phenotype to ensure proper treatment is provided.
Subject(s)
Cutis Laxa/genetics , Elastin/genetics , Adult , Child , DNA Mutational Analysis , Exons/genetics , Female , Frameshift Mutation , Heterozygote , Humans , Kazakhstan , Male , Exome SequencingABSTRACT
Ataxias with oculomotor apraxia (AOA) belong to autosomal recessive ataxias. Their common feature is oculomotor apraxia: inability to coordinate eye movements not due to muscle weakness. Next-generation sequencing (NGS) gives unique opportunities of rare disorders diagnostics and discovering of new forms, including AOA. In 2015, AOA type 4 produced by PNKP mutations was delineated in a group of Portuguese patients. We diagnosed AOA4 in a 9-year-old boy from Byelorussian family. He presented with ataxia since 2 years and deterioration in 8 years, oculomotor apraxia, dystonic hyperkinesia, dysarthria, polyneuropathy, borderline/mildly impaired intelligence, cerebellar atrophy on MRI and moderate hypercholesterolemia. Panel NGS detected two PNKP mutations: c.1123G>T (p.Gly375Trp) common in Portuguese patients, and novel c.1270_1283dupACAAACCCAGACGC (p.Ala429fs). This is one of a few world AOA4 cases and first non-Portuguese case with 'Portuguese' common mutation. The case illustrates NGS diagnostic value, particularly in rare heterogeneous disorders like AOA.
Subject(s)
Cerebellar Ataxia , High-Throughput Nucleotide Sequencing , Apraxias , Child , DNA Repair Enzymes , Humans , Male , Mutation , Phosphotransferases (Alcohol Group Acceptor)ABSTRACT
We studied chronic toxicity of a few release-active preparations: Dietressa (release-active preparation of affinity-purified antibodies to type 1 cannabinoid receptor), Divasa (releaseactive preparation containing a combination of affinity-purified antibodies to brain-specific S-100 protein and endothelial NO-synthase), Cardostin (release-active preparation containing a combination of affinity-purified antibodies to C-terminal fragment of angiotensin II type 1 receptor and endothelial NO-synthase), and Bation (release-active preparation containing a combination of affinity-purified antibodies to IFN-γ and CD4). We evaluated not only side and toxic effects, but also the relationships between these effects and pharmacological activities of the preparations. The data of preclinical toxicological studies of the release-active preparations can be used for prediction of their pharmacological activity.
Subject(s)
Antibodies/pharmacology , Appetite Depressants/pharmacology , Animals , Body Weight/drug effects , Drug Evaluation, Preclinical , Female , Male , Motor Activity/drug effects , RatsABSTRACT
The aim of the present study was to evaluate T-cadherin expression at the early developmental stages of the mouse embryo. Using in situ hybridization and immunofluorescent staining of whole embryos in combination with confocal microscopy, we found that T-cadherin expression is detected in the developing brain, starting with the E8.75 stage, and in the heart, starting with the E11.5 stage. These data suggest a possible involvement of T-cadherin in the formation of blood vessels during embryogenesis.
