Arthrogryposis, which represents a group of congenital disorders, includes various forms. One such form is amyoplasia, which most commonly presents in a sporadic form in addition to distal forms, among which hereditary cases may occur. This condition is characterized by limited joint mobility and muscle weakness, leading to limb deformities and various clinical manifestations. At present, the pathogenesis of this disease is not clearly understood, and its diagnosis is often complicated due to significant phenotypic diversity, which can result in delayed detection and, consequently, limited options for symptomatic treatment. In this study, a transcriptomic analysis of the affected muscles from patients diagnosed with amyoplasia was performed, and more than 2000 differentially expressed genes (DEGs) were identified. A functional analysis revealed disrupted biological processes, such as vacuole organization, cellular and aerobic respiration, regulation of mitochondrion organization, cellular adhesion, ATP synthesis, and others. The search for key nodes (hubs) in protein-protein interaction networks allowed for the identification of genes involved in mitochondrial processes.

Bruck syndrome is a rare autosomal recessive disorder characterized by increased bone fragility and joint contractures similar to those in arthrogryposis and is known to be associated with mutations in the FKBP10 (FKBP prolyl isomerase 10) and PLOD2 (Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2) genes. These genes encode endoplasmic reticulum proteins that play an important role in the biosynthesis of type I collagen, which in turn affects the structure and strength of connective tissues and bones in the body. Mutations are associated with disturbances in both the primary collagen chain and its post-translational formation, but the mechanism by which mutations lead to Bruck syndrome phenotypes has not been determined, not only because of the small number of patients who come to the attention of researchers but also because of the lack of disease models. In our work, we investigated the cellular effects of two forms of the wild-type PLOD2 gene, as well as the PLOD2 gene with homozygous mutation c.1885A>G (p.Thr629Ala). The synthesized genetic constructs were transfected into HEK293 cell line and human skin fibroblasts (DF2 line). The localization of PLOD2 protein in cells and the effects caused by the expression of different isoforms—long, short, and long with mutation—were analyzed. In addition, the results of the transcriptome analysis of a patient with Bruck syndrome, in whom this mutation was detected, are presented.

The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as an increase in therapeutic efficacy. A fullerene C60 conjugate (FA-PVP-C60) with polyvinylpyrrolidone (PVP) as a biocompatible spacer and folic acid (FA) as a targeting ligand for tumor cells with increased expression of folate receptors (FR) was obtained. Using 13C NMR spectroscopy, FT-IR, UV-Vis spectrometry, fluorometry and thermal analysis, the formation of the conjugate was confirmed and the nature of the binding of its components was established. The average particle sizes of the conjugate in aqueous solutions and cell culture medium were determined using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The FA-PVP-C60 showed antiradical activity against •DPPH, •OH and O2•−, but at the same time, it was shown to generate 1O2. It was found that the conjugate in the studied concentration range (up to 200 μg/mL) is non-toxic in vitro and does not affect the cell cycle. To confirm the ability of the conjugate to selectively accumulate through folate-mediated endocytosis, its uptake into cells was analyzed by flow cytometry and confocal microscopy. It was shown that the conjugate is less absorbed by A549 cells with low FR expression than by HeLa, which has a high level of expression of this receptor.

Carbon nanoparticles with antimicrobial properties, such as fullerenes, can be distinguished among the promising means of combating pathogens characterized by resistance to commercial antibiotics. However, they have a number of limitations for their use in medicine. In particular, the insolubility of carbon nanoparticles in water leads to a low biocompatibility and especially strong aggregation when transferred to liquid media. To overcome the negative factors and enhance the action of fullerenes in an extended range of applications, for example, in antimicrobial photodynamic therapy, we created new water-soluble complexes containing, in addition to C60 fullerene, purified detonation nanodiamonds (AC960) and/or polyvinylpyrrolidone (PVP). The in vitro antibacterial activity and toxicity to human cells of the three-component complex C60+AC960+PVP were analyzed in comparison with binary C60+PVP and C60+AC960. All complexes showed a low toxicity to cultured human skin fibroblasts and ECV lines, as well as significant antimicrobial activity, which depend on the type of microorganisms exposed, the chemical composition of the complex, its dosage and exposure time. Complex C60+PVP+AC960 at a concentration of 175 µg/mL showed the most stable and pronounced inhibitory microbicidal/microbiostatic effect.

Huntington's disease (HD) is one of the human neurodegenerative diseases for which there is no effective treatment. Therefore, there is a strong demand for a novel neuroprotective agent that can alleviate its course. Fullerene derivatives are considered to be such agents; however, they need to be comprehensively investigated in model organisms. In this work, neuroprotective activity of C60(OH)30 and C120O(OH)44 fullerenols was analyzed for the first time in a Drosophila transgenic model of HD. Lifespan, behavior, oxidative stress level and age-related neurodegeneration were assessed in flies with the pathogenic Huntingtin protein expression in nerve cells. Feed supplementation with hydroxylated C60 fullerene and C120O dimer oxide molecules was shown to diminish the oxidative stress level and neurodegenerative processes in the flies' brains. Thus, fullerenes displayed neuroprotective activity in this model.

The gasotransmitter hydrogen sulfide (H2S) produced by the transsulfuration pathway (TSP) is an important biological mediator, involved in many physiological and pathological processes in multiple higher organisms, including humans. Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) enzymes play a central role in H2S production and metabolism. Here, we investigated the role of H2S in learning and memory processes by exploring several Drosophila melanogaster strains with single and double deletions of CBS and CSE developed by the CRISPR/Cas9 technique. We monitored the learning and memory parameters of these strains using the mating rejection courtship paradigm and demonstrated that the deletion of the CBS gene, which is expressed predominantly in the central nervous system, and double deletions completely block short- and long-term memory formation in fruit flies. On the other hand, the flies with CSE deletion preserve short- and long-term memory but fail to exhibit long-term memory retention. Transcriptome profiling of the heads of the males from the strains with deletions in Gene Ontology terms revealed a strong down-regulation of many genes involved in learning and memory, reproductive behavior, cognition, and the oxidation–reduction process in all strains with CBS deletion, indicating an important role of the hydrogen sulfide production in these vital processes.

Parkinson's disease (PD) is a neurodegenerative disease characterised by the formation of Lewy bodies and progressive loss of dopaminergic (DA) neurons in the substantia nigra. Lewy bodies mainly consist of alpha-synuclein, which plays a critical role in the pathophysiology of PD. The alpha-synuclein is encoded by the SNCA gene and is the first identified gene associated with hereditary PD. Currently, there are at least six disease-associated mutations in alpha-synuclein that cause dominantly inherited familial forms of PD. Targeted expression of human SNCA.WT/SNCA.A30P/SNCA.A53T gene in Drosophila melanogaster over specific times employing a temperature-dependent UAS/GAL4 - GAL80 system allows for the evaluation of neurodegenerative processes. In this study, SNCA was expressed only in the adult stage of Drosophila development for 1 or 2 weeks, followed by repression of gene expression for the rest of the fly's life. It was demonstrated that the level of pathology significantly depends on the duration of alpha-synuclein expression. SNCA gene expression over a longer period of time caused the death of DA neurons, decreased levels of dopamine and locomotor ability. In this case, the observed neurodegenerative processes correlated with the accumulation of alpha-synuclein in the Drosophila brain. Importantly, repression of alpha-synuclein expression led to elimination of the soluble protein fraction, in contrast to the insoluble fraction. No further significant development of characteristic signs of pathology was observed after the alpha-synuclein expression was blocked. Thus, we suggest that reduction of alpha-synuclein expression alone contributes to slowing down the development of PD-like symptoms.

Development of carbon-based structures composed of nanoparticles with different type of orbital hybridization of carbon (sp(2), sp(3)) made it possible to create new substances with advanced biomedical properties, luminescent, and magnetic when the carbon components are modified by lanthanides for the applications in Photodynamic Therapy or Magneto-Resonance Imaging. The presented results are devoted to the synthesis, physical-chemical and synchrotron studies of water-soluble complexes of detonation nanodiamonds (particle size 4-5 nm) and fullerenols Gd@C-82(OH)(X) (X similar to 30). The association of positively charged diamonds and electro-negative fullerenols created the complexes being stable under heating (25-70 degrees C) while the assembly of fullerenols with the diamonds carrying negative surface charges was less probable. Small angle scattering of synchrotron radiation revealed the association of diamonds into chain-like structures more stable due to additional linking of diamonds via fullerenols. Due to complexing, fullerenols got magnetic resonance properties of negative contrasting substances for MRI diagnostics. The tests on biological cells showed a low toxicity of complexes which can be used as prospective biomedical materials.

Drosophila melanogaster is one of the most famous insects in biological research. It is widely used to analyse functions of different genes. The phosphatidylcholine lysophospholipase gene swiss cheese was initially shown to be important in the fruit fly nervous system. However, the role of this gene in non-nervous cell types has not been elucidated yet, and the evolutional explanation for the conservation of its function remains elusive. In this study, we analyse expression pattern and some aspects of the role of the swiss cheese gene in the fitness of Drosophila melanogaster. We describe the spatiotemporal expression of swiss cheese throughout the fly development and analyse the survival and productivity of swiss cheese mutants. We found swiss cheese to be expressed in salivary glands, midgut, Malpighian tubes, adipocytes, and male reproductive system. Dysfunction of swiss cheese results in severe pupae and imago lethality and decline of fertility, which is impressive in males. The latter is accompanied with abnormalities of male locomotor activity and courtship behaviour, accumulation of lipid droplets in testis cyst cells and decrease in spermatozoa motility. These results suggest that normal swiss cheese is important for Drosophila melanogaster fitness due to its necessity for both specimen survival and their reproductive success.

Various neurodegenerative disorders are associated with human NTE/PNPLA6 dysfunction. Mechanisms of neuropathogenesis in these diseases are far from clearly elucidated. Hereditary spastic paraplegia belongs to a type of neurodegeneration associated with NTE/PNLPLA6 and is implicated in neuron death. In this study, we used Drosophila melanogaster to investigate the consequences of neuronal knockdown of swiss cheese (sws)—the evolutionarily conserved ortholog of human NTE/PNPLA6—in vivo. Adult flies with the knockdown show longevity decline, locomotor and memory deficits, severe neurodegeneration progression in the brain, reactive oxygen species level acceleration, mitochondria abnormalities and lipid droplet accumulation. Our results suggest that SWS/NTE/PNPLA6 dysfunction in neurons induces oxidative stress and lipid metabolism alterations, involving mitochondria dynamics and lipid droplet turnover in neurodegeneration pathogenesis. We propose that there is a complex mechanism in neurological diseases such as hereditary spastic paraplegia, which includes a stress reaction, engaging mitochondria, lipid droplets and endoplasmic reticulum interplay.

Glia are crucial for the normal development and functioning of the nervous system in many animals. Insects are widely used for studies of glia genetics and physiology. Drosophila melanogaster surface glia (perineurial and subperineurial) form a blood–brain barrier in the central nervous system and blood–nerve barrier in the peripheral nervous system. Under the subperineurial glia layer, in the cortical region of the central nervous system, cortex glia encapsulate neuronal cell bodies, whilst in the peripheral nervous system, wrapping glia ensheath axons of peripheral nerves. Here, we show that the expression of the evolutionarily conserved swiss cheese gene is important in several types of glia. swiss cheese knockdown in subperineurial glia leads to morphological abnormalities of these cells. We found that the number of subperineurial glia nuclei is reduced under swiss cheese knockdown, possibly due to apoptosis. In addition, the downregulation of swiss cheese in wrapping glia causes a loss of its integrity. We reveal transcriptome changes under swiss cheese knockdown in subperineurial glia and in cortex + wrapping glia and show that the downregulation of swiss cheese in these types of glia provokes reactive oxygen species acceleration. These results are accompanied by a decline in animal mobility measured by the negative geotaxis performance assay.

Herein we report on the synthesis, structural characterization and photophysical properties of cyclometalated Pt(II) complexes [Pt(N^C)(PPh2(C6H4COOH))Cl] (where N^C ligands are 2-phenylpyridine, (2-benzofuran-3-yl)pyridine, and (2-benzo[b]tiophen-3-yl)pyridine) and their conjugates with the histidine-containing RRRRRRRRRRHVLPKVQA peptide. This peptide contains the RHVLPKVQA sequence, which is responsible for antiamyloid activity, and the Arg9 RRRRRRRRR domain, which shows improved translocation through cell membranes. The chemistry underpinning the conjugation is regioselective complexation between Pt(II) complexes and histidine residue in the peptide. The prepared conjugates have been characterized using high-resolution mass spectrometry and NMR spectroscopy. It was shown that the conjugates are easily soluble in aqueous media and display emission band profiles essentially similar to those of the starting complexes but considerably higher luminescence quantum yield and much longer phosphorescence lifetime. MTT assay on HeLa cell culture revealed no cytotoxicity up to 10 μM after 24 h of incubation. Ex vivo and in vivo neuroimaging experiments on both wild and amyloid peptide expressing strains of Drosophila melanogaster revealed that the conjugates penetrate the blood-brain barrier and are evenly distributed throughout the brain independently of the strain used.

Background. The LoeysDietz syndrome is a rare autosomal dominant connective tissue disorder characterized by the pathology of the cardiovascular system in combination with various anomalies of the musculoskeletal system. In modern literature, there is neither any information about the frequency of pathology nor any algorithm of examination and treatment for patients with this syndrome. Clinical case. The article presents a clinical observation of a 7-year-old patient with LoeysDietz syndrome with a genetically confirmed diagnosis. Discussion. This article provided a literature review, examined diagnosis issues and differential diagnosis, and presented the clinical picture of the syndrome. The main symptoms of LoeysDietz syndrome are artery aneurysms (most often in the aortic root), arterial tortuosity (mainly the vessels of the neck), hypertelorism, and bifid (split) or broad uvula. However, the combination of these symptoms is not found in all patients with this disease. Conclusions. The article emphasized the importance of a genetic verification of the disease, as well as a multidisciplinary approach to treatment with mandatory dynamic monitoring by specialists such as a cardiologist, neurologist, orthopedist, and pediatrician, which help prevent the development of complications and increase the life expectancy of this group of patients.

Глиальные клетки (ГК) являются наиболее распространенным типом клеток в центральной нервной системе. Интерес к ним значительно увеличился за последние десятилетия по мере осознания того, что глия является не только «опорными» клетками для нейронов, но также регулирует важные аспекты развития и функционирования нервной системы. У позвоночных ГК выполняют опорную, трофическую, секреторную, разграничительную и защитную функции. Несмотря на то, что нервная система Drosophila melanogaster относительно проста по своей структуре, ей присущи характеристики сложно устроенной глии млекопитающих. Схожесть глии Drosophila melanogaster и млекопитающих на молекулярном и морфологическом уровне дает возможность предположить, что исследование глии беспозвоночных позволит лучше понять основные вопросы развития глии у млекопитающих. Использование Drosophila melanogaster дает возможность изучать различные нейрон-глиальные взаимодействия в интактном организме, а использование широкого набора молекулярно-генетических методов позволяет исследовать фундаментальные вопросы природы глии. В обзоре дана классификация глиальных клеток Drosophila melanogaster, описаны известные на сегодняшний день функции всех типов глии насекомого, а также проведено сравнение функций разных типов глиальных клеток млекопитающих и дрозофилы.

Evolutionary conserved NTE gene is important for survival and functioning of nervous system cells, its dysfunction leads to various pathologies. Here we describe characteristics of different disorders induced by NTE protein activity inhibition (OPIDN) or by NTE gene mutations: hereditary spastic paraplegia (SPG39), Boucher Neuhaser, Gordon Holmes, Laurence Moon, Oliver McFarlane syndromes, Leber congenital amaurosis, pure cerebellar ataxia. Current review summarises accumulated data about clinical features of NTE associated diseases, presenting them in a historical way of biomedical studies, and observes molecular and genetic causes of these disorders.

Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease. Congenital contractures are a heterogeneous group of various diseases with different etiology and pathogenesis. The article describes a family case of hereditary sensory-motor polyneuropathy caused by a mutation with 943GA (p Arg315Trp) in the TRPV4 gene (transient receptor potential vanilloid cation channel 4, NM_021625. 4). The article presents the clinical and neurological characteristics of the patient, the results of genetic and neurophysiological examination of the patient and his parents, differential diagnosis of this disease.