41 research outputs found
Pathomechanisms of a CLCN1 Mutation Found in a Russian Family Suffering From Becker's Myotonia
Objective: Myotonia congenita (MC) is a rare muscle disease characterized by sarcolemma over-excitability inducing skeletal muscle stiffness. It can be inherited either as an autosomal dominant (Thomsen's disease) or an autosomal recessive (Becker's disease) trait. Both types are caused by loss-of-function mutations in the CLCN1 gene, encoding for ClC-1 chloride channel. We found a ClC-1 mutation, p.G411C, identified in Russian patients who suffered from a severe form of Becker's disease. The purpose of this study was to provide a solid correlation between G411C dysfunction and clinical symptoms in the affected patient. Methods: We provide clinical and genetic information of the proband kindred. Functional studies include patch-clamp electrophysiology, biotinylation assay, western blot analysis, and confocal imaging of G411C and wild-type ClC-1 channels expressed in HEK293T cells. Results: The G411C mutation dramatically abolished chloride currents in transfected HEK cells. Biochemical experiments revealed that the majority of G411C mutant channels did not reach the plasma membrane but remained trapped in the cytoplasm. Treatment with the proteasome inhibitor MG132 reduced the degradation rate of G411C mutant channels, leading to their expression at the plasma membrane. However, despite an increase in cell surface expression, no significant chloride current was recorded in the G411C-transfected cell treated with MG132, suggesting that this mutation produces non-functional ClC-1 chloride channels. Conclusion: These results suggest that the molecular pathophysiology of G411C is linked to a reduced plasma membrane expression and biophysical dysfunction of mutant channels, likely due to a misfolding defect. Chloride current abolition confirms that the mutation is responsible for the clinical phenotype
ΠΡΠ΅Π½ΠΊΠ° ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΎΡΡΠΎΡΠ½ΠΈΡ ΠΌΠΈΡΠΎΡ ΠΎΠ½Π΄ΡΠΈΠΉ ΠΌΠΎΠ½ΠΎΠ½ΡΠΊΠ»Π΅Π°ΡΠ½ΡΡ Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠΎΠ² ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΡΠΎΡΠΎΡΠ½ΠΎΠΉ ΡΠΈΡΠΎΠΌΠ΅ΡΡΠΈΠΈ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Ρ ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΡΡ ΠΏΠΎΠ΄ Π²Π»ΠΈΡΠ½ΠΈΠ΅ΠΌ ΡΠ±ΠΈΠ΄Π΅ΠΊΠ°ΡΠ΅Π½ΠΎΠ½Π°
Aim. To evaluate the functional state of mitochondria isolated from peripheral blood mononuclear leukocytes using flow cytometry in patients with chronic heart failure receiving ubidecarenone (coenzyme Q).Materials and methods. The study included 53 patients with chronic heart failure who had experienced myocardial infarction. The patients were divided into two groups: group 1 received optimally chosen standard therapy, while group 2 received optimally chosen standard therapy and ubidecarenone (βKudeviteβ). The mitochondrial membrane potential was evaluated by flow cytometry using propidium iodide and 3,3β²-dihexyloxacarbocyanine iodide (DiOC6(3)). The levels of coenzyme Q were determined using high-performance liquid chromatography with ultraviolet (UV) detection.Results. A direct correlation was established between the coenzyme Q levels in the blood plasma and the percentage of DiOC6(3)-positive cells (R = 0.39; Ρ < 0.05) in the patients with chronic heart failure. In group 1, no significant differences in the coenzyme Q levels and the percentage of DiOC6(3)-positive and DiOC6(3)-negative cells before and after the therapy were observed. In group 2, a significant increase in the proportion of DiOC6(3)-positive cells and a significant decrease in the percentage of DiOC6(3)-negative cells were revealed.Conclusion. The increase in the functional activity of mitochondria in the patients with chronic heart failure receiving ubidecarenone was identified. Flow cytometry can be used to evaluate the functional state of mitochondria and observe the efficiency of the selected therapy.Β Π¦Π΅Π»Ρ β ΠΎΡΠ΅Π½ΠΈΡΡ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠ΅ ΡΠΎΡΡΠΎΡΠ½ΠΈΠ΅ ΠΌΠΈΡΠΎΡ
ΠΎΠ½Π΄ΡΠΈΠΉ ΠΌΠΎΠ½ΠΎΠ½ΡΠΊΠ»Π΅Π°ΡΠ½ΡΡ
Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠΎΠ² ΠΏΠ΅ΡΠΈΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΡΠΎΠ²ΠΈ Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ ΠΌΠ΅ΡΠΎΠ΄Π° ΠΏΡΠΎΡΠΎΡΠ½ΠΎΠΉ ΡΠΈΡΠΎΠΌΠ΅ΡΡΠΈΠΈ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΡΡ Π½Π° ΡΠΎΠ½Π΅ ΠΏΡΠΈΠ΅ΠΌΠ° ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° ΡΠ±ΠΈΠ΄Π΅ΠΊΠ°ΡΠ΅Π½ΠΎΠ½Π° (ΠΊΠΎΡΠ½Π·ΠΈΠΌΠ° Q).ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π²ΠΊΠ»ΡΡΠ΅Π½Ρ 53 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° Ρ Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΡΡ ΠΏΠΎΡΠ»Π΅ ΠΏΠ΅ΡΠ΅Π½Π΅ΡΠ΅Π½Π½ΠΎΠ³ΠΎ ΠΈΠ½ΡΠ°ΡΠΊΡΠ° ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π°. ΠΠ°ΡΠΈΠ΅Π½ΡΡ Π±ΡΠ»ΠΈ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Ρ Π² Π΄Π²Π΅ Π³ΡΡΠΏΠΏΡ: ΠΏΠ΅ΡΠ²Π°Ρ Π³ΡΡΠΏΠΏΠ° ΠΏΠΎΠ»ΡΡΠ°Π»Π° ΡΠΎΠ»ΡΠΊΠΎ ΠΎΠΏΡΠΈΠΌΠ°Π»ΡΠ½ΠΎ ΠΏΠΎΠ΄ΠΎΠ±ΡΠ°Π½Π½ΡΡ ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΡΡ ΡΠ΅ΡΠ°ΠΏΠΈΡ, Π²ΡΠΎΡΠ°Ρ Π³ΡΡΠΏΠΏΠ° β Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎ ΠΊ ΠΎΠΏΡΠΈΠΌΠ°Π»ΡΠ½ΠΎ ΠΏΠΎΠ΄ΠΎΠ±ΡΠ°Π½Π½ΠΎΠΉ ΠΌΠ΅Π΄ΠΈΠΊΠ°ΠΌΠ΅Π½ΡΠΎΠ·Π½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΏΠΎΠ»ΡΡΠ°Π»Π° ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ ΡΠ±ΠΈΠ΄Π΅ΠΊΠ°ΡΠ΅Π½ΠΎΠ½Π° (Β«ΠΡΠ΄Π΅Π²ΠΈΡΠ°Β»). ΠΡΠ΅Π½ΠΊΠ° ΠΌΠΈΡΠΎΡ
ΠΎΠ½Π΄ΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π½ΠΎΠ³ΠΎ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»Π° ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»Π°ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΡΠΎΡΠΎΡΠ½ΠΎΠΉ ΡΠΈΡΠΎΠΌΠ΅ΡΡΠΈΠΈ Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ ΠΉΠΎΠ΄ΠΈΡΡΠΎΠ³ΠΎ ΠΏΡΠΎΠΏΠΈΠ΄ΠΈΡ ΠΈ ΠΉΠΎΠ΄ΠΈΠ΄ 3,3β-Π΄ΠΈΠ³Π΅ΠΊΡΠΈΠ»ΠΎΠΊΡΠ°ΠΊΠ°ΡΠ±ΠΎΡΠΈΠ°Π½ΠΈΠ½Π° (DiOC6(3)). ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ ΠΊΠΎΡΠ½Π·ΠΈΠΌΠ° Q Π² ΠΊΡΠΎΠ²ΠΈ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΎΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π²ΡΡΠΎΠΊΠΎΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ ΠΆΠΈΠ΄ΠΊΠΎΡΡΠ½ΠΎΠΉ Ρ
ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΠΈ Ρ ΡΠ»ΡΡΡΠ°ΡΠΈΠΎΠ»Π΅ΡΠΎΠ²ΠΎΠΉ Π΄Π΅ΡΠ΅ΠΊΡΠΈΠ΅ΠΉ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΡΠ²Π»Π΅Π½Π° ΠΏΡΡΠΌΠ°Ρ ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΠΎΠ½Π½Π°Ρ Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΡ ΠΌΠ΅ΠΆΠ΄Ρ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ΠΌ ΠΊΠΎΡΠ½Π·ΠΈΠΌΠ° Q Π² ΠΏΠ»Π°Π·ΠΌΠ΅ ΠΊΡΠΎΠ²ΠΈ ΠΈ ΠΏΡΠΎΡΠ΅Π½ΡΠΎΠΌ DiOC-ΠΏΠΎΠ·ΠΈΡΠΈΠ²Π½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ (R = 0,39; Ρ < 0,05) Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΡΡ. Π Π³ΡΡΠΏΠΏΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
ΡΠΎΠ»ΡΠΊΠΎ ΠΎΠΏΡΠΈΠΌΠ°Π»ΡΠ½ΠΎ ΠΏΠΎΠ΄ΠΎΠ±ΡΠ°Π½Π½ΡΡ ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΡΡ ΡΠ΅ΡΠ°ΠΏΠΈΡ, Π½Π΅ Π²ΡΡΠ²Π»Π΅Π½ΠΎ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΡΡ
ΡΠ°Π·Π»ΠΈΡΠΈΠΉ Π² ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠΈ ΠΊΠΎΡΠ½Π·ΠΈΠΌΠ° Q ΠΈ ΠΏΡΠΎΡΠ΅Π½ΡΠ½ΠΎΠΌ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠΈ DiOC-ΠΏΠΎΠ·ΠΈΡΠΈΠ²Π½ΡΡ
ΠΈ DiOC-Π½Π΅Π³Π°ΡΠΈΠ²Π½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ Π΄ΠΎ Π½Π°ΡΠ°Π»Π° ΠΈ ΠΏΠΎΡΠ»Π΅ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ. Π Π³ΡΡΠΏΠΏΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ ΡΠ±ΠΈΠ΄Π΅ΠΊΠ°ΡΠ΅Π½ΠΎΠ½Π°, ΠΏΠΎΡΠ»Π΅ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π½Π°Π±Π»ΡΠ΄Π°Π»ΠΎΡΡ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΠΎΠ΅ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ Π΄ΠΎΠ»ΠΈ DiOC-ΠΏΠΎΠ·ΠΈΡΠΈΠ²Π½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ ΠΈ ΡΠΌΠ΅Π½ΡΡΠ΅Π½ΠΈΠ΅ Π΄ΠΎΠ»ΠΈ DiOC-Π½Π΅Π³Π°ΡΠΈΠ²Π½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΌΠΈΡΠΎΡ
ΠΎΠ½Π΄ΡΠΈΠΉ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΡΡ Π½Π° ΡΠΎΠ½Π΅ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠΌ ΡΠ±ΠΈΠ΄Π΅ΠΊΠ°ΡΠ΅Π½ΠΎΠ½Π°. ΠΠ΅ΡΠΎΠ΄ ΠΏΡΠΎΡΠΎΡΠ½ΠΎΠΉ ΡΠΈΡΠΎΠΌΠ΅ΡΡΠΈΠΈ ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΎΡΡΠΎΡΠ½ΠΈΡ ΠΌΠΈΡΠΎΡ
ΠΎΠ½Π΄ΡΠΈΠΉ ΠΈ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΈΠΌΠ΅Π½ΡΠ΅ΠΌΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ
Biallelic MFSD2A variants associated with congenital microcephaly, developmental delay, and recognizable neuroimaging features
Major Facilitator Superfamily Domain containing 2a (MFSD2A) is an essential endothelial lipid transporter at the blood-brain barrier. Biallelic variants affecting function in MFSD2A cause autosomal recessive primary microcephaly 15 (MCPH15, OMIM# 616486). We sought to expand our knowledge of the phenotypic spectrum of MCPH15 and demonstrate the underlying mechanism of inactivation of the MFSD2A transporter. We carried out detailed analysis of the clinical and neuroradiological features of a series of 27 MCPH15 cases, including eight new individuals from seven unrelated families. Genetic investigation was performed through exome sequencing (ES). Structural insights on the human Mfsd2a model and in-vitro biochemical assays were used to investigate the functional impact of the identified variants. All patients had primary microcephaly and severe developmental delay. Brain MRI showed variable degrees of white matter reduction, ventricular enlargement, callosal hypodysgenesis, and pontine and vermian hypoplasia. ES led to the identification of six novel biallelic MFSD2A variants (NG_053084.1, NM_032793.5: c.556+1G>A, c.748G>T; p.(Val250Phe), c.750_753del; p.(Cys251SerfsTer3), c.977G>A; p.(Arg326His), c.1386_1435del; p.(Gln462HisfsTer17), and c.1478C>T; p.(Pro493Leu)) and two recurrent variants (NM_032793.5: c.593C>T; p.(Thr198Met) and c.476C>T; p.(Thr159Met)). All these variants and the previously reported NM_032793.5: c.490C>A; p.(Pro164Thr) resulted in either reduced MFSD2A expression and/or transport activity. Our study further delineates the phenotypic spectrum of MCPH15, refining its clinical and neuroradiological characterization and supporting that MFSD2A deficiency causes early prenatal brain developmental disruption. We also show that poor MFSD2A expression despite normal transporter activity is a relevant pathomechanism in MCPH15
Clinical and genetic characteristics of CharcotβMarieβTooth disease type 4D (type Lom) in Russia
Introduction. CharcotβMarieβTooth disease type 4D is a hereditary demyelinating neuropathy, that occurs with the high frequency in patients of Roma origin. It is characterized by early onset at the age of 2β10 years and hearing impairment, manifested by the 3rd decade of life.Aim of the study. To describe the clinical and genetic characteristics of CharcotβMarieβTooth disease type 4D in Russian patients of Roma origin.Materials and methods. For 14 probands from unrelated families of Roma origin with a clinical diagnosis of CharcotβMarieβTooth disease, genetic tests for the pathogenic variants c. 442C>T in the NDRG1 gene and c. 3325C>T in the SH3TC2 gene was carried out. For 8 patients with CharcotβMarieβTooth disease type 4D, detailed clinical and electrophysiological examination was performed.Results. In 11 families of Roma origin, the c. 442C>T pathogenic variant in the NDRG1 gene in a homozygous state was detected, which accounted for 79 % all observed Roma patients with CharcotβMarieβTooth disease. There are 12 of the 14 tested families live in the European part of Russia, 7 of them are from nearby regions. The average age of onset was 3.3 years. The first symptom in 7 of 8 patients was gait disturbances. At the time of examination (age range 6β19 years), all patients showed marked hypotrophy and weakness of the feet, lower leg, hands muscles, feet deformities, reduction or loss of tendon reflexes.Discussion. Due to the detection of only one pathogenic variant in most Russian patients of Roma origin with CharcotβMarieβTooth disease, the knowledge of the ethnicity of a proband with early myelinopathy can significantly simplify the confirmation of the diagnosis on the molecular level
Optimization of microwave drying conditions of two banana varieties using response surface methodology
ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΠΏΠ΅ΡΠ²ΠΎΠ³ΠΎ ΡΠΎΡΡΠΈΠΉΡΠΊΠΎΠ³ΠΎ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° Ρ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ ΡΠ΅ΡΠ΅ΠΏΠ½ΠΎΠ»ΠΈΡΠ΅Π²ΡΡ Π΄ΠΈΡΠΌΠΎΡΡΠΈΠΉ-Π³Π»ΡΡ ΠΎΡΡ-Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΉ Π²Π΅ΡΡ Π½ΠΈΡ ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ΅ΠΉ, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΠΌ ΠΌΡΡΠ°ΡΠΈΠ΅ΠΉ Π² Π³Π΅Π½Π΅ PAX3
Craniofacial dysmorphia-deafness-anomalies of the upper limbs is a rare autosomal dominant syndrome caused by variants in the PAX3 gene. In contrast to the two main nosological forms β Waardenburg syndrome types 1 and 3, caused by variants in this gene, the syndrome of craniofacial dysmorphias-deafness-anomalies of the upper limbs is not characterized by the presence of hair hypopigmentation and heterochromia of the iris, while congenital contractures of the wrist and interphalangeal joints of the hands. There is a description in the literature of three patients from the same family with a syndrome caused by the c.141C>G(p.Asn47Lys) variant in the PAX3 gene. Aim of the work is to present the clinical and genetic characteristics of the first Russian patient with the syndrome of craniofacial dysmorphia-deafness-anomalies of the upper extremities.Molecular genetic analysis of a 1-year and 10-month-old proband with phenotypic signs of the syndrome of craniofacial dysmorphia-deafness-anomalies of the upper limbs was carried out by direct automatic Sanger sequencing of the entire coding sequence of the PAX3 gene. Genotyping of parents was carried out by direct automatic sequencing according to Sanger. Sequencing was carried out on an ABIPrism3500Ρ
I instrument (Applied Biosystems) in accordance with the manufacturerβs protocol; primer sequences were selected according to the reference sequence of the target regions of the PAX3 gene (NM_181459.4).In Russian proband 1 year 10 months-old, the phenotypic characteristics of the syndrome of craniofacial dysmorphia-deafness-anomalies of the upper limbs did not differ from the description of sick family members presented in the literature. A molecular genetic study revealed a heterozygous variant c.141C>G(p.Asn47Lys) in the PAX3 gene in the presented patient.Π‘ΠΈΠ½Π΄ΡΠΎΠΌ ΡΠ΅ΡΠ΅ΠΏΠ½ΠΎ-Π»ΠΈΡΠ΅Π²ΡΡ
Π΄ΠΈΡΠΌΠΎΡΡΠΈΠΉ-Π³Π»ΡΡ
ΠΎΡΡ-Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΉ Π²Π΅ΡΡ
Π½ΠΈΡ
ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ΅ΠΉ β ΡΠ΅Π΄ΠΊΠΈΠΉ Π°ΡΡΠΎΡΠΎΠΌΠ½ΠΎ-Π΄ΠΎΠΌΠΈΠ½Π°Π½ΡΠ½ΡΠΉ ΡΠΈΠ½Π΄ΡΠΎΠΌ, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΠΉ Π²Π°ΡΠΈΠ°Π½ΡΠ°ΠΌΠΈ Π² Π³Π΅Π½Π΅ PAX3. Π ΠΎΡΠ»ΠΈΡΠΈΠ΅ ΠΎΡ 2 ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
Π½ΠΎΠ·ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠΎΡΠΌ β ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΠΠ°Π°ΡΠ΄Π΅Π½Π±ΡΡΠ³Π° 1-Π³ΠΎ ΠΈ 3-Π³ΠΎ ΡΠΈΠΏΠΎΠ², ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠ°ΠΌΠΈ Π² Π΄Π°Π½Π½ΠΎΠΌ Π³Π΅Π½Π΅, Π΄Π»Ρ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΡΠ΅ΡΠ΅ΠΏΠ½ΠΎ-Π»ΠΈΡΠ΅Π²ΡΡ
Π΄ΠΈΡΠΌΠΎΡΡΠΈΠΉ-Π³Π»ΡΡ
ΠΎΡΡ-Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΉ Π²Π΅ΡΡ
Π½ΠΈΡ
ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ΅ΠΉ Π½Π΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ½ΠΎ Π½Π°Π»ΠΈΡΠΈΠ΅ Π³ΠΈΠΏΠΎΠΏΠΈΠ³ΠΌΠ΅Π½ΡΠ°ΡΠΈΠΈ Π²ΠΎΠ»ΠΎΡ ΠΈ Π³Π΅ΡΠ΅ΡΠΎΡ
ΡΠΎΠΌΠΈΠΈ ΡΠ°Π΄ΡΠΆΠΊΠΈ, ΠΏΡΠΈ ΡΡΠΎΠΌ ΠΎΡΠΌΠ΅ΡΠ°ΡΡΡΡ Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΠ΅ ΠΊΠΎΠ½ΡΡΠ°ΠΊΡΡΡΡ Π»ΡΡΠ΅Π·Π°ΠΏΡΡΡΠ½ΡΡ
ΠΈ ΠΌΠ΅ΠΆΡΠ°Π»Π°Π½Π³ΠΎΠ²ΡΡ
ΡΡΡΡΠ°Π²ΠΎΠ² ΠΊΠΈΡΡΠ΅ΠΉ. Π Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ΅ ΠΈΠΌΠ΅Π΅ΡΡΡ ΠΎΠΏΠΈΡΠ°Π½ΠΈΠ΅ 3 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΈΠ· ΠΎΠ΄Π½ΠΎΠΉ ΡΠ΅ΠΌΡΠΈ Ρ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΠΌ Π²Π°ΡΠΈΠ°Π½ΡΠΎΠΌ c.141C>G(p.Asn47Lys) Π² Π³Π΅Π½Π΅ PAX3.Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β ΠΏΡΠ΅Π΄ΡΡΠ°Π²ΠΈΡΡ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΠΏΠ΅ΡΠ²ΠΎΠ³ΠΎ ΡΠΎΡΡΠΈΠΉΡΠΊΠΎΠ³ΠΎ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° Ρ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ ΡΠ΅ΡΠ΅ΠΏΠ½ΠΎ-Π»ΠΈΡΠ΅Π²ΡΡ
Π΄ΠΈΡΠΌΠΎΡΡΠΈΠΉ-Π³Π»ΡΡ
ΠΎΡΡ-Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΉ Π²Π΅ΡΡ
Π½ΠΈΡ
ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ΅ΠΉ. ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· Ρ ΠΏΡΠΎΠ±Π°Π½Π΄Π° Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ 1 Π³ΠΎΠ΄ 10 ΠΌΠ΅Ρ Ρ ΡΠ΅Π½ΠΎΡΠΈΠΏΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΏΡΠΈΠ·Π½Π°ΠΊΠ°ΠΌΠΈ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΡΠ΅ΡΠ΅ΠΏΠ½ΠΎ-Π»ΠΈΡΠ΅Π²ΡΡ
Π΄ΠΈΡΠΌΠΎΡΡΠΈΠΉ-Π³Π»ΡΡ
ΠΎΡΡ-Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΉ Π²Π΅ΡΡ
Π½ΠΈΡ
ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΡΡΠΌΠΎΠ³ΠΎ Π°Π²ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎ Π‘ΡΠ½Π³Π΅ΡΡ Π²ΡΠ΅ΠΉ ΠΊΠΎΠ΄ΠΈΡΡΡΡΠ΅ΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ Π³Π΅Π½Π° PAX3. ΠΠ΅Π½ΠΎΡΠΈΠΏΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΠ΄ΠΈΡΠ΅Π»Π΅ΠΉ ΡΠ°ΠΊΠΆΠ΅ ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΡΡΠΌΠΎΠ³ΠΎ Π°Π²ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎ Π‘ΡΠ½Π³Π΅ΡΡ. Π‘Π΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Π½Π° ΠΏΡΠΈΠ±ΠΎΡΠ΅ ABIPrism3500Ρ
I (Applied Biosystems) Π² ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΈΠΈ Ρ ΠΏΡΠΎΡΠΎΠΊΠΎΠ»ΠΎΠΌ ΡΠΈΡΠΌΡ-ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΠΈΡΠ΅Π»Ρ, ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΏΡΠ°ΠΉΠΌΠ΅ΡΠΎΠ² Π±ΡΠ»ΠΈ ΠΏΠΎΠ΄ΠΎΠ±ΡΠ°Π½Ρ ΡΠΎΠ³Π»Π°ΡΠ½ΠΎ ΡΠ΅ΡΠ΅ΡΠ΅Π½ΡΠ½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΡΠ΅Π»Π΅Π²ΡΡ
ΡΡΠ°ΡΡΠΊΠΎΠ² Π³Π΅Π½Π° PAX3 (NM_181459.4). Π£ ΡΠΎΡΡΠΈΠΉΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΠ±Π°Π½Π΄Π° Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ 1 Π³ΠΎΠ΄ 10 ΠΌΠ΅Ρ ΡΠ΅Π½ΠΎΡΠΈΠΏΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΡΠ΅ΡΠ΅ΠΏΠ½ΠΎ-Π»ΠΈΡΠ΅Π²ΡΡ
Π΄ΠΈΡΠΌΠΎΡΡΠΈΠΉ-Π³Π»ΡΡ
ΠΎΡΡ-Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΉ Π²Π΅ΡΡ
Π½ΠΈΡ
ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ΅ΠΉ Π½Π΅ ΠΎΡΠ»ΠΈΡΠ°Π»ΠΈΡΡ ΠΎΡ ΡΠ°ΠΊΠΎΠ²ΡΡ
Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
ΡΠ»Π΅Π½ΠΎΠ² ΡΠ΅ΠΌΡΠΈ, ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π½ΡΡ
Π² Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ΅. ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π²ΡΡΠ²ΠΈΠ»ΠΎ Π³Π΅ΡΠ΅ΡΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΡΠΉ Π²Π°ΡΠΈΠ°Π½Ρ c.141C>G(p.Asn47Lys) Π² Π³Π΅Π½Π΅PAX3 Ρ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π½ΠΎΠ³ΠΎ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°. ΠΠ° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ Π°Π½Π°Π»ΠΈΠ·Π° ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ ΡΠ΅Π½ΠΎΡΠΈΠΏΠ° Π½Π°Π±Π»ΡΠ΄Π°Π΅ΠΌΠΎΠ³ΠΎ Π½Π°ΠΌΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° ΠΈ Π΅Π΄ΠΈΠ½ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΡΠ΅ΠΌΠ΅ΠΉΠ½ΠΎΠ³ΠΎ ΡΠ»ΡΡΠ°Ρ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΡΠ΅ΡΠ΅ΠΏΠ½ΠΎ-Π»ΠΈΡΠ΅Π²ΡΡ
Π΄ΠΈΡΠΌΠΎΡΡΠΈΠΉ-Π³Π»ΡΡ
ΠΎΡΡ-Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΉ Π²Π΅ΡΡ
Π½ΠΈΡ
ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ΅ΠΉ, ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π½ΠΎΠ³ΠΎ Π² Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ΅, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΠΎΠ³ΠΎ Π²Π°ΡΠΈΠ°Π½ΡΠΎΠΌ c.141C>G(p.Asn47Lys) Π² Π³Π΅Π½Π΅ PAX3, ΠΎΠ±ΠΎΠ·Π½Π°ΡΠ΅Π½ ΡΠΏΠ΅ΠΊΡΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠΈΠΌΠΏΡΠΎΠΌΠΎΠ² ΡΡΠΎΠΉ Π½ΠΎΠ·ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΎΡΠΌ
ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΡΠ°Π½Π½Π΅ΠΉ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ½ΡΠ΅ΡΠ°Π»ΠΎΠΏΠ°ΡΠΈΠΈ II ΡΠΈΠΏΠ°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΠΎΠΉ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ SCN2A
Background.Β A large number of single gene disorders with seizures in clinical picture has been described. Among them, a special place is held by early-onset epileptic encephalopathies (EEE) β a genetically diverse group of disorders characterized by manifestation of seizures in the first 2 years of life and severe progressing course. Currently, 58 genetic variants of EEE has been identified.The objectiveΒ is to analyze the incidence, clinical and genetic characteristic of type II EEE in a sample of patients from Russia identified by whole exome sequencing using next generation sequencing.Materials and methods.Β The patient sample included 67 children (35 boys and 32 girls) with ages varying from 4 months to 10 years. All patients underwent neurological examination using the standard techniques. Monitoring of electroencephalography (EEG) was performed in accordance with the International 10β20 system. For magnetic resonance imaging, tomographs with magnetic induction of 1.5 and 3.0 T were used. The identified changes were confirmed by Sanger sequencing using DNA from the patients and their parents.Results.Β In total, 67 patients with EEE were diagnosed, 8 of which had causational mutations in the SCN2A gene: p.Leu1611Pro (c.4832T>C), p.Cys728* (c.2184C>A), p.Arg607* (c.1819C>T), p.Val1325Ile (c.623T>C), p.Leu419Met (c.1255T>A), p.Asp1487Glu (c.4461C>A), p.Val208Ala (c.3973G>A), p.Gln1211Lys (c.3631G>A). Analysis of parent DNA had shown that all mutations appeared de novo. At the time of disease onset, all patients had multiregional epileptiform activity per EEG. Focal seizures, myoclonic seizures, and epileptic spasms were the most common types of seizures in the patients. The majority of patients (5/8) had diffuse muscular hypotonia. All patients had pronounced mental deficiency. All patients received more than 2 therapy regimens (including hormonal therapy and ketogenic diet) but full remission wasnβt obtained. In some patients, partial positive dynamic was registered with hormonal therapy and sodium channel blockers. Various mutations in the SCN2A gene caused a similar clinical picture but had different functional significance which determined the effectiveness of anti-epileptic therapy.Conclusion.Β Identification of the mutated genes causing EEE and further study of their function are important for selection of therapeutic approach to epilepsy treatment.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅.Β ΠΠΏΠΈΡΠ°Π½ΠΎ Π±ΠΎΠ»ΡΡΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΌΠΎΠ½ΠΎΠ³Π΅Π½Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΠ°ΡΡΠΈΠ½Π΅ ΠΊΠΎΡΠΎΡΡΡ
Π½Π°Π±Π»ΡΠ΄Π°ΡΡΡΡ ΡΡΠ΄ΠΎΡΠΎΠ³ΠΈ. Π‘ΡΠ΅Π΄ΠΈ Π½ΠΈΡ
ΠΎΡΠΎΠ±ΠΎΠ΅ ΠΌΠ΅ΡΡΠΎ Π·Π°Π½ΠΈΠΌΠ°ΡΡ ΡΠ°Π½Π½ΠΈΠ΅ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ½ΡΠ΅ΡΠ°Π»ΠΎΠΏΠ°ΡΠΈΠΈ (Π ΠΠ) β Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈ Π³Π΅ΡΠ΅ΡΠΎΠ³Π΅Π½Π½Π°Ρ Π³ΡΡΠΏΠΏΠ° Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΡΡΠΈΡ
ΡΡ ΠΌΠ°Π½ΠΈΡΠ΅ΡΡΠ°ΡΠΈΠ΅ΠΉ ΡΡΠ΄ΠΎΡΠΎΠ³ Π΄ΠΎ 2-Π»Π΅ΡΠ½Π΅Π³ΠΎ Π²ΠΎΠ·ΡΠ°ΡΡΠ° ΠΈ ΡΡΠΆΠ΅Π»ΡΠΌ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΡΡΡΠΈΠΌ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ΠΌ. Π Π½Π°ΡΡΠΎΡΡΠ΅ΠΌΡ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Ρ 58 Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² Π ΠΠ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΒ β Π°Π½Π°Π»ΠΈΠ· ΡΠ°ΡΡΠΎΡΡ Π²ΡΡΡΠ΅ΡΠ°Π΅ΠΌΠΎΡΡΠΈ ΠΈ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊ Π ΠΠ II ΡΠΈΠΏΠ° Π² Π²ΡΠ±ΠΎΡΠΊΠ΅ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΈΠ· ΠΏΠΎΠΏΡΠ»ΡΡΠΈΠΈ Π ΠΎΡΡΠΈΠΈ, Π²ΡΡΠ²Π»Π΅Π½Π½ΡΡ
Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΊΠ·ΠΎΠΌΠ° Π½ΠΎΠ²ΠΎΠ³ΠΎ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΡ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ.Β ΠΡΠ±ΠΎΡΠΊΠ° Π±ΠΎΠ»ΡΠ½ΡΡ
Π²ΠΊΠ»ΡΡΠ°Π»Π° 67 Π΄Π΅ΡΠ΅ΠΉ (35 ΠΌΠ°Π»ΡΡΠΈΠΊΠΎΠ² ΠΈ 32 Π΄Π΅Π²ΠΎΡΠΊΠΈ) Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ ΠΎΡ 4 ΠΌΠ΅Ρ Π΄ΠΎ 10 Π»Π΅Ρ. ΠΡΠ΅ΠΌ Π±ΠΎΠ»ΡΠ½ΡΠΌ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Π½Π΅Π²ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΎΡΠΌΠΎΡΡ ΠΏΠΎ ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΠΎΠΉ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ΅. ΠΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³ Π²ΠΈΠ΄Π΅ΠΎ-ΡΠ»Π΅ΠΊΡΡΠΎΡΠ½ΡΠ΅ΡΠ°Π»ΠΎΠ³ΡΠ°ΡΠΈΠΈ (ΠΠΠ) ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ»ΠΈ Π² ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΈΠΈ Ρ ΠΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΠΎΠΉ 10β20. ΠΠ»Ρ ΠΌΠ°Π³Π½ΠΈΡΠ½ΠΎ-ΡΠ΅Π·ΠΎΠ½Π°Π½ΡΠ½ΠΎΠΉ ΡΠΎΠΌΠΎΠ³ΡΠ°ΡΠΈΠΈ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π° ΠΏΡΠΈΠΌΠ΅Π½ΡΠ»ΠΈ Π°ΠΏΠΏΠ°ΡΠ°ΡΡ c ΠΈΠ½Π΄ΡΠΊΡΠΈΠ΅ΠΉ ΠΌΠ°Π³Π½ΠΈΡΠ½ΠΎΠ³ΠΎ ΠΏΠΎΠ»Ρ 1,5 ΠΈ 3,0 Π’Π». ΠΡΡΠ²Π»Π΅Π½Π½ΡΠ΅ Π·Π°ΠΌΠ΅Π½Ρ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π°Π»ΠΈ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΏΠΎ Π‘ΡΠ½Π³Π΅ΡΡ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΠΠ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΈ ΠΈΡ
ΡΠΎΠ΄ΠΈΡΠ΅Π»Π΅ΠΉ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ.Β ΠΡΠ»ΠΈ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠΎΠ²Π°Π½Ρ 67 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π ΠΠ, 8 ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ
ΠΈΠΌΠ΅Π»ΠΈ ΠΊΠ°ΡΠ·Π°ΡΠΈΠ²Π½ΡΠ΅ ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π³Π΅Π½Π΅ SCN2A: p.Leu1611Pro (c.4832T>C), p.Cys728* (c.2184C>A), p.Arg607* (c.1819C>T), p.Val1325Ile (c.623T>C), p.Leu419Met (c.1255T>A), p.Asp1487Glu (c.4461C>A), p.Val208Ala (c.3973G>A), p.Gln1211Lys (c.3631G>A). ΠΠ½Π°Π»ΠΈΠ· ΡΠΎΠ΄ΠΈΡΠ΅Π»ΡΡΠΊΠΎΠΉ ΠΠΠ ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ Π²ΡΠ΅ ΠΌΡΡΠ°ΡΠΈΠΈ Π²ΠΎΠ·Π½ΠΈΠΊΠ»ΠΈ de novo. ΠΠ° ΠΌΠΎΠΌΠ΅Π½Ρ Π΄Π΅Π±ΡΡΠ° ΠΏΡΠΈΡΡΡΠΏΠΎΠ² Π²ΡΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΡ ΠΈΠΌΠ΅Π»ΠΈ ΠΌΡΠ»ΡΡΠΈΡΠ΅Π³ΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΡΠΎΡΠΌΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΠΎ Π΄Π°Π½Π½ΡΠΌ ΠΠΠ. Π§Π°ΡΠ΅ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΎΡΠΌΠ΅ΡΠ°Π»ΠΈΡΡ ΡΠΎΠΊΠ°Π»ΡΠ½ΡΠ΅ ΠΏΡΠΈΡΡΡΠΏΡ, ΠΌΠΈΠΎΠΊΠ»ΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΡΠΈΡΡΡΠΏΡ ΠΈ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠΏΠ°Π·ΠΌΡ. Π£ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π° Π±ΠΎΠ»ΡΠ½ΡΡ
(5/8) Π½Π°Π±Π»ΡΠ΄Π°Π»Π°ΡΡ Π΄ΠΈΡΡΡΠ·Π½Π°Ρ ΠΌΡΡΠ΅ΡΠ½Π°Ρ Π³ΠΈΠΏΠΎΡΠΎΠ½ΠΈΡ. Π£ Π²ΡΠ΅Ρ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΎΡΠΌΠ΅ΡΠ°Π»Π°ΡΡ Π²ΡΡΠ°ΠΆΠ΅Π½Π½Π°Ρ ΡΠΌΡΡΠ²Π΅Π½Π½Π°Ρ ΠΎΡΡΡΠ°Π»ΠΎΡΡΡ. ΠΡΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΡ ΠΏΠΎΠ»ΡΡΠ°Π»ΠΈ Π±ΠΎΠ»Π΅Π΅ 2 ΡΡ
Π΅ΠΌ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ (Π²ΠΊΠ»ΡΡΠ°Ρ Π³ΠΎΡΠΌΠΎΠ½Π°Π»ΡΠ½ΡΡ ΡΠ΅ΡΠ°ΠΏΠΈΡ ΠΈ ΠΊΠ΅ΡΠΎΠ³Π΅Π½Π½ΡΡ Π΄ΠΈΠ΅ΡΡ), ΠΎΠ΄Π½Π°ΠΊΠΎ ΠΏΠΎΠ»Π½ΠΎΠΉ ΡΠ΅ΠΌΠΈΡΡΠΈΠΈ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΠΈ Π΄ΠΎΡΡΠΈΡΡ Π½Π΅ ΡΠ΄Π°Π»ΠΎΡΡ. Π£ ΡΠ°ΡΡΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½Π° ΡΠ°ΡΡΠΈΡΠ½Π°Ρ ΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½Π°Ρ Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠ° ΠΏΡΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠΈ Π³ΠΎΡΠΌΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΈ Π±Π»ΠΎΠΊΠ°ΡΠΎΡΠΎΠ² Π½Π°ΡΡΠΈΠ΅Π²ΡΡ
ΠΊΠ°Π½Π°Π»ΠΎΠ². Π Π°Π·Π½ΡΠ΅ ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π³Π΅Π½Π΅ SCN2A ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡ ΠΊ ΡΡ
ΠΎΠ΄Π½ΠΎΠΉ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΠ°ΡΡΠΈΠ½Π΅, Π½ΠΎ ΠΈΠΌΠ΅ΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ Π·Π½Π°ΡΠΈΠΌΠΎΡΡΡ, ΡΡΠΎ ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅Ρ ΡΠ°Π·Π½ΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠΎΡΠΈΠ²ΠΎΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅.Β ΠΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ Π³Π΅Π½Π°, ΠΌΡΡΠ°ΡΠΈΠΈ Π² ΠΊΠΎΡΠΎΡΠΎΠΌ ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡ ΠΊ Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΡ Π ΠΠ, ΠΈ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅Π΅ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π΅Π³ΠΎ ΡΡΠ½ΠΊΡΠΈΠΈ ΠΎΡΠ΅Π½Ρ Π²Π°ΠΆΠ½Ρ Π² Π²ΡΠ±ΠΎΡΠ΅ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Π° ΠΊ Π»Π΅ΡΠ΅Π½ΠΈΡ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΠΈ
ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΠΌΠΈΠΎΠΏΠ°ΡΠΈΠΈ ΠΠΎΠ½Π°ΠΊΠ° (GNE-ΠΌΠΈΠΎΠΏΠ°ΡΠΈΠΈ) Ρ ΡΠΎΡΡΠΈΠΉΡΠΊΠΈΡ Π±ΠΎΠ»ΡΠ½ΡΡ
Clinical and genetic characteristics of 9patients with Nonaka myopathy (GNE-myopathy) from Russia are presented. As a result of exom sequencing, 11 different mutations were revealed in the GNE gene, 8 of which were described earlier, and 3 β Π‘ys203Ser, Met263CysfsTer and deletion of the whole gene β were detected for the first time. The peculiarities of clinical manifestation of Russian patients with GNE-myopathy are described.ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ 9 Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ ΠΌΠΈΠΎΠΏΠ°ΡΠΈΠ΅ΠΉ ΠΠΎΠ½Π°ΠΊΠ° (GNE-ΠΌΠΈΠΎΠΏΠ°ΡΠΈΡ) ΠΈΠ· Π ΠΎΡΡΠΈΠΈ. Π ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΊΠ·ΠΎΠΌΠ° Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½ΠΎ 11 ΡΠ°Π·Π½ΡΡ
ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ GNE, 8 ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ
Π±ΡΠ»ΠΈ ΠΎΠΏΠΈΡΠ°Π½Ρ ΡΠ°Π½Π΅Π΅, Π‘ys203Ser, Met263CysfsTer ΠΈ Π΄Π΅Π»Π΅ΡΠΈΡ ΡΠ΅Π»ΠΎΠ³ΠΎ Π³Π΅Π½Π° β Π²ΡΡΠ²Π»Π΅Π½Ρ Π²ΠΏΠ΅ΡΠ²ΡΠ΅. ΠΠΏΠΈΡΠ°Π½Ρ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ Π²ΡΠ±ΠΎΡΠΊΠΈ
Consensus concept of modern effective therapy for Duchenne muscular dystrophy
Duchenne muscular dystrophy is a genetic orphan neuromuscular disease caused by a mutation in the DMD gene encodβ ing the protein dystrophin. As a result of developing and progressive muscle damage and atrophy, childrenlose the abilβ ity to walk, develop respiratory and cardiac disorders. The core elements of good care standards are early diagnosis, prevention and treatment of osteoporosis, daily physical therapy, regular rehabilitation, glucocorticosteroids, and control of heart andlung function. The clinical effect of new targeted pathogenetic therapies for Duchenne muscular dystrophy, restoring synthesis of full or truncated dystrophin, depend on their appropriate combination with existing standards of care. Β© 2023 ABV-Press Publishing House. All rights reserved
ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ Π±ΠΎΠ»Π΅Π·Π½ΠΈ Π¨Π°ΡΠΊΠΎβΠΠ°ΡΠΈβΠ’ΡΡΠ° ΡΠΈΠΏΠ° 4D (ΡΠΈΠΏΠ° Lom) Π² Π ΠΎΡΡΠΈΠΈ
Introduction. CharcotβMarieβTooth disease type 4D is a hereditary demyelinating neuropathy, that occurs with the high frequency in patients of Roma origin. It is characterized by early onset at the age of 2β10 years and hearing impairment, manifested by the 3rd decade of life.Aim of the study. To describe the clinical and genetic characteristics of CharcotβMarieβTooth disease type 4D in Russian patients of Roma origin.Materials and methods. For 14 probands from unrelated families of Roma origin with a clinical diagnosis of CharcotβMarieβTooth disease, genetic tests for the pathogenic variants c. 442C>T in the NDRG1 gene and c. 3325C>T in the SH3TC2 gene was carried out. For 8 patients with CharcotβMarieβTooth disease type 4D, detailed clinical and electrophysiological examination was performed.Results. In 11 families of Roma origin, the c. 442C>T pathogenic variant in the NDRG1 gene in a homozygous state was detected, which accounted for 79 % all observed Roma patients with CharcotβMarieβTooth disease. There are 12 of the 14 tested families live in the European part of Russia, 7 of them are from nearby regions. The average age of onset was 3.3 years. The first symptom in 7 of 8 patients was gait disturbances. At the time of examination (age range 6β19 years), all patients showed marked hypotrophy and weakness of the feet, lower leg, hands muscles, feet deformities, reduction or loss of tendon reflexes.Discussion. Due to the detection of only one pathogenic variant in most Russian patients of Roma origin with CharcotβMarieβTooth disease, the knowledge of the ethnicity of a proband with early myelinopathy can significantly simplify the confirmation of the diagnosis on the molecular level.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΠΎΠ»Π΅Π·Π½Ρ Π¨Π°ΡΠΊΠΎβΠΠ°ΡΠΈβΠ’ΡΡΠ° ΡΠΈΠΏΠ° 4D β Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½Π°Ρ Π΄Π΅ΠΌΠΈΠ΅Π»ΠΈΠ½ΠΈΠ·ΠΈΡΡΡΡΠ°Ρ Π½Π΅ΠΉΡΠΎΠΏΠ°ΡΠΈΡ, Π²ΡΡΡΠ΅ΡΠ°ΡΡΠ°ΡΡΡ Ρ Π½Π°ΠΈΠ±ΠΎΠ»ΡΡΠ΅ΠΉ ΡΠ°ΡΡΠΎΡΠΎΠΉ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΡΡΠ³Π°Π½ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΡ ΠΈ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΡΡΠ°ΡΡΡ ΡΠ°Π½Π½ΠΈΠΌ Π΄Π΅Π±ΡΡΠΎΠΌ Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ 2β10 Π»Π΅Ρ ΠΈ Π½Π°ΡΡΡΠ΅Π½ΠΈΠ΅ΠΌ ΡΠ»ΡΡ
Π°, ΠΏΡΠΎΡΠ²Π»ΡΡΡΠΈΠΌΡΡ ΠΊ 3-ΠΉ Π΄Π΅ΠΊΠ°Π΄Π΅ ΠΆΠΈΠ·Π½ΠΈ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΎΠΏΠΈΡΠ°ΡΡ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ Π±ΠΎΠ»Π΅Π·Π½ΠΈ Π¨Π°ΡΠΊΠΎβΠΠ°ΡΠΈβΠ’ΡΡΠ° ΡΠΈΠΏΠ° 4D Ρ ΡΠΎΡΡΠΈΠΉΡΠΊΠΈΡ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΡΡΠ³Π°Π½ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΡ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΠΎΠ±Π°Π½Π΄Π°ΠΌ ΠΈΠ· 14 Π½Π΅ΡΠΎΠ΄ΡΡΠ²Π΅Π½Π½ΡΡ
ΡΠ΅ΠΌΠ΅ΠΉ ΡΡΠ³Π°Π½ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΡ Ρ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌ Π΄ΠΈΠ°Π³Π½ΠΎΠ·ΠΎΠΌ Β«Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½Π°Ρ ΠΌΠΎΡΠΎΡΠ½ΠΎ-ΡΠ΅Π½ΡΠΎΡΠ½Π°Ρ Π½Π΅ΠΉΡΠΎΠΏΠ°ΡΠΈΡΒ» ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ ΠΏΠΎΠΈΡΠΊ ΠΏΠ°ΡΠΎΠ³Π΅Π½Π½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² c. 442C>T Π² Π³Π΅Π½Π΅ NDRG1 ΠΈ Ρ. 3325C>T Π² Π³Π΅Π½Π΅ SH3TC2. Π£ 8 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π±ΠΎΠ»Π΅Π·Π½ΡΡ Π¨Π°ΡΠΊΠΎβΠΠ°ΡΠΈβΠ’ΡΡΠ° ΡΠΈΠΏΠ° 4D ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π° ΠΎΡΠ΅Π½ΠΊΠ° ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΡΠ°ΡΡΡΠ°, Ρ 3 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² β Π°Π½Π°Π»ΠΈΠ· ΡΠ»Π΅ΠΊΡΡΠΎΠ½Π΅ΠΉΡΠΎΠΌΠΈΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π΄Π°Π½Π½ΡΡ
.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π 11 ΡΠ΅ΠΌΡΡΡ
ΡΡΠ³Π°Π½ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΡ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ ΠΏΠ°ΡΠΎΠ³Π΅Π½Π½ΡΠΉ Π²Π°ΡΠΈΠ°Π½Ρ c. 442C>T Π² Π³Π΅Π½Π΅ NDRG1 Π² Π³ΠΎΠΌΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΠΎΠΌ ΡΠΎΡΡΠΎΡΠ½ΠΈΠΈ, ΡΡΠΎ ΡΠΎΡΡΠ°Π²ΠΈΠ»ΠΎ 79 % Π²ΡΠ΅Ρ
ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΡΡ
ΡΡΠ³Π°Π½ Ρ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΌΠΎΡΠΎΡΠ½ΠΎ-ΡΠ΅Π½ΡΠΎΡΠ½ΠΎΠΉ Π½Π΅ΠΉΡΠΎΠΏΠ°ΡΠΈΠ΅ΠΉ. ΠΠ· 14 ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΡΡ
ΡΠ΅ΠΌΠ΅ΠΉ 12 ΠΏΡΠΎΠΆΠΈΠ²Π°ΡΡ Π² Π΅Π²ΡΠΎΠΏΠ΅ΠΉΡΠΊΠΎΠΉ ΡΠ°ΡΡΠΈ Π ΠΎΡΡΠΈΠΈ, 7 ΠΈΠ· Π½ΠΈΡ
β Π² Π±Π»ΠΈΠ·ΠΊΠΎΡΠ°ΡΠΏΠΎΠ»ΠΎΠΆΠ΅Π½Π½ΡΡ
ΡΡΠ±ΡΠ΅ΠΊΡΠ°Ρ
Π ΠΎΡΡΠΈΠΉΡΠΊΠΎΠΉ Π€Π΅Π΄Π΅ΡΠ°ΡΠΈΠΈ. ΠΠΎΠ·ΡΠ°ΡΡ Π΄Π΅Π±ΡΡΠ° Π±ΠΎΠ»Π΅Π·Π½ΠΈ ΡΠΎΡΡΠ°Π²ΠΈΠ» Π² ΡΡΠ΅Π΄Π½Π΅ΠΌ 3,3 Π³ΠΎΠ΄Π°. Π£ 7 ΠΈΠ· 8 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² 1-ΠΌ ΡΠΈΠΌΠΏΡΠΎΠΌΠΎΠΌ Π±ΡΠ»ΠΎ Π½Π°ΡΡΡΠ΅Π½ΠΈΠ΅ ΠΏΠΎΡ
ΠΎΠ΄ΠΊΠΈ. ΠΠ° ΠΌΠΎΠΌΠ΅Π½Ρ ΠΎΡΠΌΠΎΡΡΠ° (Π²ΠΎΠ·ΡΠ°ΡΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΎΡ 6 Π΄ΠΎ 19 Π»Π΅Ρ) Ρ Π²ΡΠ΅Ρ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Π²ΡΡΠ²Π»Π΅Π½Ρ Π²ΡΡΠ°ΠΆΠ΅Π½Π½Π°Ρ Π³ΠΈΠΏΠΎΡΡΠΎΡΠΈΡ ΠΈ ΡΠ»Π°Π±ΠΎΡΡΡ ΠΌΡΡΡ ΡΡΠΎΠΏ, Π³ΠΎΠ»Π΅Π½Π΅ΠΉ, ΠΊΠΈΡΡΠ΅ΠΉ, Π΄Π΅ΡΠΎΡΠΌΠ°ΡΠΈΡ ΡΡΠΎΠΏ, ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΠΈΠ»ΠΈ ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ ΡΡΡ
ΠΎΠΆΠΈΠ»ΡΠ½ΡΡ
ΡΠ΅ΡΠ»Π΅ΠΊΡΠΎΠ² Ρ Π½ΠΎΠ³.ΠΠ±ΡΡΠΆΠ΄Π΅Π½ΠΈΠ΅. Π£ΡΠΈΡΡΠ²Π°Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΈ ΡΠΎΠ³ΠΎ ΠΆΠ΅ ΠΏΠ°ΡΠΎΠ³Π΅Π½Π½ΠΎΠ³ΠΎ Π²Π°ΡΠΈΠ°Π½ΡΠ° Ρ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π° ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΡΡΠ³Π°Π½ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΡ Ρ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΌΠΎΡΠΎΡΠ½ΠΎΠΉ ΡΠ΅Π½ΡΠΎΡΠ½ΠΎΠΉ Π½Π΅ΠΉΡΠΎΠΏΠ°ΡΠΈΠ΅ΠΉ, Π·Π½Π°Π½ΠΈΠ΅ ΡΡΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠΈΠ½Π°Π΄Π»Π΅ΠΆΠ½ΠΎΡΡΠΈ ΠΏΡΠΎΠ±Π°Π½Π΄Π° Ρ ΡΠ°Π½Π½Π΅ΠΉ ΠΌΠΈΠ΅Π»ΠΈΠ½ΠΎΠΏΠ°ΡΠΈΠ΅ΠΉ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΡΠΏΡΠΎΡΠ°Π΅Ρ ΠΏΠΎΠΈΡΠΊ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠΈΡΠΈΠ½Ρ Π±ΠΎΠ»Π΅Π·Π½ΠΈ