67 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
ΠΡΠΎΠΊΡΠΈΠΌΠ°Π»ΡΠ½Π°Ρ ΡΠΏΠΈΠ½Π°Π»ΡΠ½Π°Ρ ΠΌΡΡΠ΅ΡΠ½Π°Ρ Π°ΡΡΠΎΡΠΈΡ ΡΠΈΠΏΠΎΠ² IβIV: ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ
Proximal spinal muscular atrophy (SMA) types I-IV is the most common autosomal recessive neuromuscular disease caused by mutations inΒ the SMN1 gene encoding the survival motor neuron protein. It is characterized by progressive muscle weakness due to injury of the motor neuronsΒ of the anterior horns of the spinal cord. The classification of the disease is based on the time of its onset, severity, and survival. The detectionΒ of the major mutation of exon 7 and/or 8 deletion in the SMN1 gene is a qualitative reliable and sensitive diagnostic test. The SMN1 geneΒ has the almost complete homolog SMN2 gene, which hampers the analysis of heterozygous carriage of the disease. So the determination of theΒ carriage status is based on the quantitative analysis of the number of SMN1 gene copies. The paper covers problems and new possibilities in themolecular genetic diagnosis of proximal SMA.ΠΡΠΎΠΊΡΠΈΠΌΠ°Π»ΡΠ½Π°Ρ ΡΠΏΠΈΠ½Π°Π»ΡΠ½Π°Ρ ΠΌΡΡΠ΅ΡΠ½Π°Ρ Π°ΡΡΠΎΡΠΈΡ (Π‘ΠΠ) ΡΠΈΠΏΠΎΠ² IβIV β Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠ°ΡΡΠΎΠ΅ Π°ΡΡΠΎΡΠΎΠΌΠ½ΠΎ-ΡΠ΅ΡΠ΅ΡΡΠΈΠ²Π½ΠΎΠ΅ Π½Π΅ΠΉΡΠΎΠΌΡΡΠ΅ΡΠ½ΠΎΠ΅Β Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅, Π²ΡΠ·ΡΠ²Π°Π΅ΠΌΠΎΠ΅ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ SMN1, ΠΊΠΎΠ΄ΠΈΡΡΡΡΠ΅ΠΌ Π±Π΅Π»ΠΎΠΊ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ ΠΌΠΎΡΠΎΠ½Π΅ΠΉΡΠΎΠ½ΠΎΠ². Π₯Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΠ΅ΡΡΡ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΡΡΡΠ΅ΠΉ ΠΌΡΡΠ΅ΡΠ½ΠΎΠΉ ΡΠ»Π°Π±ΠΎΡΡΡΡ Π²ΡΠ»Π΅Π΄ΡΡΠ²ΠΈΠ΅ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΡ Π΄Π²ΠΈΠ³Π°ΡΠ΅Π»ΡΠ½ΡΡ
Π½Π΅ΠΉΡΠΎΠ½ΠΎΠ² ΠΏΠ΅ΡΠ΅Π΄Π½ΠΈΡ
ΡΠΎΠ³ΠΎΠ² ΡΠΏΠΈΠ½Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π°. ΠΠ»Π°ΡΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΠΎΡΠ½ΠΎΠ²Π°Π½Π° Π½Π° Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ Π΅Π³ΠΎ Π½Π°ΡΠ°Π»Π°, ΡΡΠΆΠ΅ΡΡΠΈ ΡΠ΅ΡΠ΅Π½ΠΈΡ ΠΈ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΆΠΈΠ·Π½ΠΈ. ΠΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΌΠ°ΠΆΠΎΡΠ½ΠΎΠΉ ΠΌΡΡΠ°ΡΠΈΠΈ Π΄Π΅Π»Π΅ΡΠΈΠΈ ΡΠΊΠ·ΠΎΠ½ΠΎΠ² 7 ΠΈ/ΠΈΠ»ΠΈ 8 Π³Π΅Π½Π° SMN1 ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠΌ, Π½Π°Π΄Π΅ΠΆΠ½ΡΠΌ ΠΈ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΠΌ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΡΠ΅ΡΡΠΎΠΌ.Β ΠΠ΅Π½ SMN1 ΠΈΠΌΠ΅Π΅Ρ ΠΏΠΎΡΡΠΈ ΠΏΠΎΠ»Π½ΡΠΉ Π³ΠΎΠΌΠΎΠ»ΠΎΠ³ β Π³Π΅Π½ SMN2, ΡΡΠΎ Π·Π°ΡΡΡΠ΄Π½ΡΠ΅Ρ Π°Π½Π°Π»ΠΈΠ· Π³Π΅ΡΠ΅ΡΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΠΎΠ³ΠΎ Π½ΠΎΡΠΈΡΠ΅Π»ΡΡΡΠ²Π° Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ. ΠΠΎΡΡΠΎΠΌΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΡΠ°ΡΡΡΠ° Π½ΠΎΡΠΈΡΠ΅Π»Ρ ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΎ Π½Π° ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΌ Π°Π½Π°Π»ΠΈΠ·Π΅ ΡΠΈΡΠ»Π° ΠΊΠΎΠΏΠΈΠΉ Π³Π΅Π½Π° SMN1. Π ΡΠ°Π±ΠΎΡΠ΅ ΠΎΡΠ²Π΅ΡΠ°ΡΡΡΡ ΠΏΡΠΎΠ±Π»Π΅ΠΌΡ ΠΈ Π½ΠΎΠ²ΡΠ΅ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ Π² ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ΅ ΠΏΡΠΎΠΊΡΠΈΠΌΠ°Π»ΡΠ½ΠΎΠΉ Π‘ΠΠ
Differential diagnosis of myopathy and multiple epiphysal dysplasia caused by mutations in the <i>COMP</i> gene in children
Background. Multiple epiphysal dysplasia (MED) type 1 (OMIM: 132400) is one of 7 genetic variants of this group of skeletal dysplasias described to date. The disease is caused by mutations in the COMP gene located on chromosome 19p13.1. The presence of muscle hypotonia and ligamentous laxity, as well as a moderate increase in the level of creatinephosphokinase activity, can lead to misdiagnosis of myopathy.Objective: to analyze the clinical and genetic characteristics of type 1 MED caused by mutations in the COMP gene in a series of Russian patients. Differential diagnosis was focused on the distinctive features of the disorder and hereditary myopathies.Materials and methods. We observed 8 patients from 7 families aged 7 to 15 years with MED type 1 caused by heterozygous mutations in the COMP gene. To confirm the diagnosis, the following methods were used: genealogical analysis, clinical examination, neurological examination with psycho-emotional testing, radiography and targeted sequencing of a panel consisting of 166 genes responsible for the development of inherited skeletal pathology.Results. Case history, clinical, radiological and genetic characteristics of 8 patients with MED type 1 caused by mutations in the COMP gene were analyzed. The first clinical manifestations of the disease were recorded from the age of 2β3 years and were characterized by gait disturbances, muscle weakness, difficulties with climbing stairs, frequent falls when walking, the inability to get up from the floor and from a squatting position and hypermobility of the joints. Electroneuromyographic study did not reveal the signs of miopathy. In two patients, a moderate increase in the creatinekinase level of up to 250β360 u / l was found. All patients were surveyed by neurologists for several years with a clinical diagnosis of congenital myopathy. At the age of 5β6 years patients COMPlained knee and ankle pain, which was assumed as rheumatic arthropathy. X-ray examination revealed typical signs of deficient ossification of the epiphyses. The next-generation sequencing analysis revealed seven single nucleotide variants in the COMP gene that lead to MED type 1. Three of the found variants here identified for the first time. As previously described, the majority of nucleotide variants (six out of seven) were localized in the 8β14 exons of the COMP gene and led to amino acid substitutions in calmodulin-like protein domain repeats, and only one substitution was localized in the C-terminal region of the protein molecule.Conclusion. In most patients with MED caused by mutations in the COMP gene, the first symptoms of the disease are gait disturbance, muscle weakness, and GowersΒ» maneuvers. The presence of these symptoms, along with a moderate increase in the level of creatinephosphokinase activity, often precedes the onset of clinical manifestations of skeletal dysplasia, leading to a misdiagnosis with myopathies. Accession of expressive arthralgias to these symptoms was mistakenly identified as reactive arthritis. X-ray examination of patientsβ long bones helps to suspect the presence of MED. This X-ray imaging shows specific signs of epiphyses damage. A molecular-genetic analysis needs to be done to diagnose the genetic variant, caused by mutations in gene COMP
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
ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ Π½ΠΎΠ²ΡΡ Π°Π»Π»Π΅Π»ΡΠ½ΡΡ Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΠΌΠΎΠ²Π°ΡβΠΠΈΠ»ΡΠΎΠ½Π°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΠΎΠ³ΠΎ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ ZEB2
To date, a large number of monogenic diseases and syndromes, in the clinical picture of which there are convulsions, a psycho-speech development delay and dysmorphic features have been described. One of the hereditary syndromes with a specific phenotype is the MovatβWilson syndrome. To diagnose the syndrome, a set of survey methods was used: genealogical analysis, neurological examination, evaluation of intellectual development with the help of psychological tests, and sequencing of the new generation exome. As a result of sequencing exome on the panel of genes responsible for the emergence of hereditary epilepsy, two patients of different sex at the age of 10 and 5 years were identified with previously not described mutations in the ZEB2 gene in the heterozygous state. Clinical manifestations of the disease in these patients were of varying degrees of severity, which can be explained in terms of the functional significance of the changes detected. The variety of clinical manifestations of the same disease leads to considerable difficulties in diagnosing, however, due to the introduction of the nextgeneration sequencing in medical practice, the effectiveness of diagnosing hereditary diseases and syndromes, the verification of which has been difficult for a long time, has increased significantly.Π Π½Π°ΡΡΠΎΡΡΠ΅ΠΌΡ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΠΎΠΏΠΈΡΠ°Π½ΠΎ Π±ΠΎΠ»ΡΡΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΌΠΎΠ½ΠΎΠ³Π΅Π½Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΠΈ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠ², Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΠ°ΡΡΠΈΠ½Π΅ ΠΊΠΎΡΠΎΡΡΡ
Π½Π°Π±Π»ΡΠ΄Π°ΡΡΡΡ ΡΡΠ΄ΠΎΡΠΎΠ³ΠΈ, Π·Π°Π΄Π΅ΡΠΆΠΊΠ° ΡΠ΅ΠΌΠΏΠΎΠ² ΠΏΡΠΈΡ
ΠΎΡΠ΅ΡΠ΅Π²ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΈ Π΄ΠΈΠ·ΠΌΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ΅ΡΡΡ ΡΡΡΠΎΠ΅Π½ΠΈΡ. ΠΠ΄Π½ΠΈΠΌ ΠΈΠ· Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΡΡ
ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠ² ΡΠΎ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΡΠ΅Π½ΠΎΡΠΈΠΏΠΎΠΌ ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠΈΠ½Π΄ΡΠΎΠΌ ΠΠΎΠ²Π°ΡβΠΠΈΠ»ΡΠΎΠ½Π°. ΠΠ»Ρ Π΅Π³ΠΎ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π»ΠΈ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ: Π³Π΅Π½Π΅Π°Π»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ·, Π½Π΅Π²ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΎΡΠΌΠΎΡΡ, ΠΎΡΠ΅Π½ΠΊΡ ΠΈΠ½ΡΠ΅Π»Π»Π΅ΠΊΡΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΏΡΠΈΡ
ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ΅ΡΡΠΎΠ² ΠΈ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΊΠ·ΠΎΠΌΠ° Π½ΠΎΠ²ΠΎΠ³ΠΎ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΡ. Π ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΊΠ·ΠΎΠΌΠ° ΠΏΠΎ ΠΏΠ°Π½Π΅Π»ΠΈ Π³Π΅Π½ΠΎΠ², ΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΡΡ
Π·Π° Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΠ΅ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΡΡ
ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΠΉ, Π²ΡΡΠ²Π»Π΅Π½Ρ 2 Π±ΠΎΠ»ΡΠ½ΡΡ
ΡΠ°Π·Π½ΠΎΠ³ΠΎ ΠΏΠΎΠ»Π° Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ 10 ΠΈ 5 Π»Π΅Ρ Ρ ΡΠ°Π½Π΅Π΅ Π½Π΅ ΠΎΠΏΠΈΡΠ°Π½Π½ΡΠΌΠΈ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ ZEB2 Π² Π³Π΅ΡΠ΅ΡΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΠΎΠΌ ΡΠΎΡΡΠΎΡΠ½ΠΈΠΈ. ΠΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ Ρ ΡΡΠΈΡ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Π±ΡΠ»ΠΈ ΡΠ°Π·Π½ΠΎΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΡΡΠΈ, ΡΡΠΎ ΠΌΠΎΠΆΠ½ΠΎ ΠΎΠ±ΡΡΡΠ½ΠΈΡΡ Ρ ΡΠΎΡΠΊΠΈ Π·ΡΠ΅Π½ΠΈΡ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ Π·Π½Π°ΡΠΈΠΌΠΎΡΡΠΈ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ. Π Π°Π·Π½ΠΎΠΎΠ±ΡΠ°Π·ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΈ ΡΠΎΠ³ΠΎ ΠΆΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΡΠΌ ΡΡΡΠ΄Π½ΠΎΡΡΡΠΌ Π² ΠΏΠΎΡΡΠ°Π½ΠΎΠ²ΠΊΠ΅ Π΄ΠΈΠ°Π³Π½ΠΎΠ·Π°, ΠΎΠ΄Π½Π°ΠΊΠΎ Π±Π»Π°Π³ΠΎΠ΄Π°ΡΡ Π²Π½Π΅Π΄ΡΠ΅Π½ΠΈΡ Π²ΠΎ Π²ΡΠ°ΡΠ΅Π±Π½ΡΡ ΠΏΡΠ°ΠΊΡΠΈΠΊΡ ΠΌΠ΅ΡΠΎΠ΄Π° ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΊΠ·ΠΎΠΌΠ° Π½ΠΎΠ²ΠΎΠ³ΠΎ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΠΈ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠ², Π²Π΅ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΠΊΠΎΡΠΎΡΡΡ
Π΄ΠΎΠ»Π³ΠΎΠ΅ Π²ΡΠ΅ΠΌΡ Π±ΡΠ»Π° Π·Π°ΡΡΡΠ΄Π½Π΅Π½Π°, Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΠΏΠΎΠ²ΡΡΠΈΠ»Π°ΡΡ
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
ΠΠΎΠ²ΡΠΉ Π°Π»Π»Π΅Π»ΡΠ½ΡΠΉ Π²Π°ΡΠΈΠ°Π½Ρ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΠΎΠΉ Π°ΡΡΠΎΡΠΎΠΌΠ½ΠΎ-ΡΠ΅ΡΠ΅ΡΡΠΈΠ²Π½ΠΎΠΉ ΠΌΠΎΡΠΎΡΠ½ΠΎ-ΡΠ΅Π½ΡΠΎΡΠ½ΠΎΠΉ Π½Π΅ΠΉΡΠΎΠΏΠ°ΡΠΈΠΈ 2S ΡΠΈΠΏΠ°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΠΉ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ IGHMBP2
Hereditary motor and sensory neuropathy (HMSN, CharcotβMarieβTooth disease) is a group of genetically heterogeneous disordersΒ with more than 80 genes linked to different phenotypes, including IGHMBP2 gene responsible for HMSN type 2S (OMIM 616155). UntilΒ recently, mutations in IGHMBP2 were exclusively associated with neonatal distal spinal muscular atrophy with respiratory distressΒ (SMARD1, OMIM 604320). A case report presents a boy with infant onset decreased distal muscle tone and weakness, distal wasting andΒ deformation in legs and hands, areflexia and decreased sensation without respiratory involvement; at age seven he had severe fixed kypho-scoliosis. EMG revealed signs distal axonal neuropathy. The exsome sequencing confirmed the allelic variant of two compound heterozygousΒ mutations in gene IGHMBP2: known missens mutation Ρ.1616Π‘>Π’ (Ρ.Ser539Leu) in exone 11 and a novel deletionΒ Ρ.2601_2602delGA in exone 13. The diagnosis of infant HMSN type 2S was confirmed. The phenotype of HMSN type 2S and its diagnosticsΒ differences between SMARD1 are discussed.ΠΠ°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΡΠ΅ ΠΌΠΎΡΠΎΡΠ½ΠΎ-ΡΠ΅Π½ΡΠΎΡΠ½ΡΠ΅ Π½Π΅ΠΉΡΠΎΠΏΠ°ΡΠΈΠΈ (ΠΠΠ‘Π, Π±ΠΎΠ»Π΅Π·Π½Ρ Π¨Π°ΡΠΊΠΎβΠΠ°ΡΠΈβΠ’ΡΡΠ°) β Π³ΡΡΠΏΠΏΠ° Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈ Π³Π΅ΡΠ΅ΡΠΎΠ³Π΅Π½Π½ΡΡ
Β ΡΠΎΡΡΠΎΡΠ½ΠΈΠΉ, Π΄Π»Ρ ΠΊΠΎΡΠΎΡΡΡ
ΠΎΠΏΠΈΡΠ°Π½Ρ ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π±ΠΎΠ»Π΅Π΅ ΡΠ΅ΠΌ 80 Π³Π΅Π½Π°Ρ
, Π²ΠΊΠ»ΡΡΠ°Ρ Π³Π΅Π½ IGHMBP2, ΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΡΠΉ Π·Π° ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΠΠΠ‘ΠΒ ΡΠΈΠΏΠ° 2S (OMIM: 616 155). ΠΠΎ Π½Π°ΡΡΠΎΡΡΠ΅Π³ΠΎ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π³Π΅Π½Π΅ IGHMBP2 ΡΠ²ΡΠ·ΡΠ²Π°Π»ΠΈ ΠΈΡΠΊΠ»ΡΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Ρ Π½Π΅ΠΎΠ½Π°ΡΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΡΡΠ°Π»ΡΠ½ΠΎΠΉ ΡΠΏΠΈΠ½Π°Π»ΡΠ½ΠΎΠΉ Π°ΠΌΠΈΠΎΡΡΠΎΡΠΈΠ΅ΠΉ Ρ Π΄ΡΡ
Π°ΡΠ΅Π»ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΡΡ (spinal muscular atrophy with respiratory distress, SMARD1, OMIM:Β 604 320). ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠ»ΡΡΠ°ΠΉ ΠΌΠ°Π»ΡΡΠΈΠΊΠ° 7 Π»Π΅Ρ Ρ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ΠΌ Π² ΠΌΠ»Π°Π΄Π΅Π½ΡΠ΅ΡΡΠ²Π΅ ΡΠ½ΠΈΠΆΠ΅Π½Π½ΠΎΠ³ΠΎ ΠΌΡΡΠ΅ΡΠ½ΠΎΠ³ΠΎ ΡΠΎΠ½ΡΡΠ° ΠΈ Π°ΡΡΠΎΡΠΈΠΈΒ ΠΌΡΡΡ Π΄ΠΈΡΡΠ°Π»ΡΠ½ΡΡ
ΠΎΡΠ΄Π΅Π»ΠΎΠ² ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ΅ΠΉ, Π΄Π΅ΡΠΎΡΠΌΠ°ΡΠΈΠ΅ΠΉ ΠΊΠΈΡΡΠ΅ΠΉ ΠΈ ΡΡΠΎΠΏ, Π°ΡΠ΅ΡΠ»Π΅ΠΊΡΠΈΠ΅ΠΉ ΠΈ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΠΌΠΈ Π½Π°ΡΡΡΠ΅Π½ΠΈΡΠΌΠΈ ΠΏΠΎ ΠΏΠΎΠ»ΠΈΠ½Π΅Π²ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΌΡ ΡΠΈΠΏΡ Π±Π΅Π· ΠΏΡΠΈΠ·Π½Π°ΠΊΠΎΠ² Π΄ΡΡ
Π°ΡΠ΅Π»ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΠΈ Π·Π° Π²ΡΠ΅ Π²ΡΠ΅ΠΌΡ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΡ, Π° ΡΠ°ΠΊΠΆΠ΅ Ρ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΌ ΡΠΈΠΊΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌ ΠΊΠΈΡΠΎΡΠΊΠΎΠ»ΠΈΠΎΠ·ΠΎΠΌ. ΠΡΠΈ ΡΠ»Π΅ΠΊΡΡΠΎΠΌΠΈΠΎΠ³ΡΠ°ΡΠΈΠΈ Π² ΡΠ°Π½Π½Π΅ΠΌ Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ Π±ΡΠ»Π° Π²ΡΡΠ²Π»Π΅Π½Π° Π΄ΠΈΡΡΠ°Π»ΡΠ½Π°Ρ Π°ΠΊΡΠΎΠ½Π°Π»ΡΠ½Π°Ρ Π½Π΅ΠΉΡΠΎΠΏΠ°ΡΠΈΡ. ΠΡΠΈ ΡΠΊΠ·ΠΎΠΌΠ½ΠΎΠΌ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Ρ 2 ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π³Π΅Π½Π΅ IGHMBP2 Π² ΠΊΠΎΠΌΠΏΠ°ΡΠ½Π΄-Π³Π΅ΡΠ΅ΡΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΠΎΠΌ ΡΠΎΡΡΠΎΡΠ½ΠΈΠΈ: ΠΎΠΏΠΈΡΠ°Π½Π½Π°Ρ ΡΠ°Π½Π΅Π΅Β ΠΌΠΈΡΡΠ΅Π½Ρ-ΠΌΡΡΠ°ΡΠΈΡ Ρ.1616Π‘>Π’ (Ρ. Ser539Leu) Π² ΡΠΊΠ·ΠΎΠ½Π΅ 11 ΠΈ Π²ΡΡΠ²Π»Π΅Π½Π½Π°Ρ Π²ΠΏΠ΅ΡΠ²ΡΠ΅ Π΄Π΅Π»Π΅ΡΠΈΡ ΡΠΎ ΡΠ΄Π²ΠΈΠ³ΠΎΠΌ ΡΠ°ΠΌΠΊΠΈ ΡΡΠΈΡΡΠ²Π°Π½ΠΈΡΒ Ρ.2601_2602delGA Π² ΡΠΊΠ·ΠΎΠ½Π΅ 13. ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠ΄ΠΈΠ»ΠΎ Π΄ΠΈΠ°Π³Π½ΠΎΠ· Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΠΎΠΉ Π°ΠΊΡΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ ΠΏΠΎΠ»ΠΈΠ½Π΅ΠΉΡΠΎΠΏΠ°ΡΠΈΠΈ Ρ ΠΌΡΡΠ°ΡΠΈΠ΅ΠΉ Π² Π³Π΅Π½Π΅ IGHMBP2. ΠΠ±ΡΡΠΆΠ΄Π°ΡΡΡΡ ΡΠ΅Π½ΠΎΡΠΈΠΏ ΠΠΠ‘Π ΡΠΈΠΏΠ° 2S, ΡΠ»ΠΎΠΆΠ½ΠΎΡΡΠΈ Π΅Π³ΠΎ ΡΠ°Π½Π½Π΅ΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅Β Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ Π΄ΠΈΠ°Π³Π½ΠΎΠ·Π° ΡΠΎ SMARD1
ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ Π₯-ΡΡΠ΅ΠΏΠ»Π΅Π½Π½ΠΎΠΉ ΡΠΌΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΎΡΡΡΠ°Π»ΠΎΡΡΠΈ 102βΠ³ΠΎ ΡΠΈΠΏΠ°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΠΎΠΉ Π²Π½ΠΎΠ²Ρ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΠΌΠΈ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ DDX3X (OMIM:300958)
Introduction. X-linked mental retardation 102 type caused by novel mutations in the DDX3X gene is one of the most common monogenic variants of intellectual deficiency in women.Purpose of the study. Description of the clinical and genetic characteristics of Russian female patients with type 102 mental retardation due to newly identified mutations.Materials and methods. The diagnosis of mental retardation of type 102 was established on the basis of the features of clinical manifestations and the detection of the mutations in the DDX3X gene as a result of exome sequencing and subsequent confirmation of the identified variants of Sanger sequencing.Results. A description is given of the clinical and genetic characteristics of two female patients with type 102 X-linked mental retardation due newly to identified mutations p.1703C> G and c.113A> G (NM_001193416) in the DDX3X gene in the heterozygous state. New features of the phenotype are described. The mechanism of the appearance of clinical and genetic correlations is suggested, which can be used as a prognostic marker of the development of the disease.Conclusion. Clinical and genetic characteristics of two patients with mutations in the DDX3X gene that violate the amino acid sequence of different protein regions with different severity of clinical manifestations are described. The results obtained may testify in favor of the existence of a dependence of the severity of the phenotype on the localization and nature of mutations in the gene and determine the relevance of further research aimed at searching for clinical and genetic correlations.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. Π₯-ΡΡΠ΅ΠΏΠ»Π΅Π½Π½Π°Ρ ΡΠΌΡΡΠ²Π΅Π½Π½Π°Ρ ΠΎΡΡΡΠ°Π»ΠΎΡΡΡ 102βΠ³ΠΎ ΡΠΈΠΏΠ°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½Π°Ρ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ DDX3X, β ΠΎΠ΄ΠΈΠ½ ΠΈΠ· Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΡΡ
ΠΌΠΎΠ½ΠΎΠ³Π΅Π½Π½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² ΠΈΠ½ΡΠ΅Π»Π»Π΅ΠΊΡΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ Π΄Π΅ΡΠΈΡΠΈΡΠ° Ρ Π»ΠΈΡ ΠΆΠ΅Π½ΡΠΊΠΎΠ³ΠΎ ΠΏΠΎΠ»Π°.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΎΠΏΠΈΡΠ°Π½ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊ Π»ΠΈΡ ΠΆΠ΅Π½ΡΠΊΠΎΠ³ΠΎ ΠΏΠΎΠ»Π° Π² Π ΠΎΡΡΠΈΠΈ Ρ ΡΠΌΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΎΡΡΡΠ°Π»ΠΎΡΡΡΡ 102βΠ³ΠΎ ΡΠΈΠΏΠ°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΡ
Π²Π½ΠΎΠ²Ρ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΠΌΠΈ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠΈΠ°Π³Π½ΠΎΠ· ΡΠΌΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΎΡΡΡΠ°Π»ΠΎΡΡΠΈ 102βΠ³ΠΎ ΡΠΈΠΏΠ° ΡΡΡΠ°Π½Π°Π²Π»ΠΈΠ²Π°Π»ΡΡ Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ ΠΈ Π²ΡΡΠ²Π»Π΅Π½Π½ΠΎΠΉ ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π³Π΅Π½Π΅ DDX3X ΠΏΠΎ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ°ΠΌ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΊΠ·ΠΎΠΌΠ° Π½ΠΎΠ²ΠΎΠ³ΠΎ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΡ ΠΈ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠ΅Π³ΠΎ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π΅Π½ΠΈΡ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² Π°Π²ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΏΠΎ Π‘ΡΠ½Π³Π΅ΡΡ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΎ ΠΎΠΏΠΈΡΠ°Π½ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊ 2 Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΆΠ΅Π½ΡΠΊΠΎΠ³ΠΎ ΠΏΠΎΠ»Π° Ρ Π₯-ΡΡΠ΅ΠΏΠ»Π΅Π½Π½ΠΎΠΉ ΡΠΌΡΡΠ²Π΅Π½- Π½ΠΎΠΉ ΠΎΡΡΡΠ°Π»ΠΎΡΡΡΡ 102βΠ³ΠΎ ΡΠΈΠΏΠ°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΠΎΠΉ Π²Π½ΠΎΠ²Ρ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΠΌΠΈ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Ρ.1703Π‘>G ΠΈ c.113A>G (NM_001193416) Π² Π³Π΅Π½Π΅ DDX3X Π² Π³Π΅ΡΠ΅ΡΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΠΎΠΌ ΡΠΎΡΡΠΎΡΠ½ΠΈΠΈ. ΠΠΏΠΈΡΠ°Π½Ρ Π½ΠΎΠ²ΡΠ΅ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΡΠ΅Π½ΠΎΡΠΈΠΏΠ°. ΠΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌ Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΡ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΠΉ, ΠΊΠΎΡΠΎΡΡΠΉ ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ ΠΊΠ°ΠΊ ΠΏΡΠΎΠ³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΌΠ°ΡΠΊΠ΅Ρ ΡΠ°Π·Π²ΠΈΡΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΏΠΈΡΠ°Π½Ρ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ 2 Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ DDX3X, Π½Π°ΡΡΡΠ°ΡΡΠΈΠΌΠΈ Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡΠ½ΡΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
Π±Π΅Π»ΠΊΠΎΠ²ΡΡ
ΡΠ΅Π³ΠΈΠΎΠ½ΠΎΠ², Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΠΎΠΉ ΡΡΠΆΠ΅ΡΡΡΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΌΠΎΠ³ΡΡ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΠΎΠ²Π°ΡΡ Π² ΠΏΠΎΠ»ΡΠ·Ρ ΡΡΡΠ΅ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΡ Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΡΡΠΈ ΡΠ΅Π½ΠΎΡΠΈΠΏΠ° ΠΎΡ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΈ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ° ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ ΠΈ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»ΠΈΠ²Π°ΡΡ Π°ΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ, Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΡΡ
Π½Π° ΠΏΠΎΠΈΡΠΊ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΠΉ
ΠΠ°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½Π°Ρ ΠΌΠΎΡΠΎΡΠ½ΠΎ-ΡΠ΅Π½ΡΠΎΡΠ½Π°Ρ Π½Π΅ΠΉΡΠΎΠΏΠ°ΡΠΈΡ, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½Π°Ρ ΠΌΡΡΠ°ΡΠΈΠ΅ΠΉ Π² Π³Π΅Π½Π΅ NEFL, Π² ΡΠ΅ΠΌΡΠ΅ ΠΈΠ· ΠΠ°ΡΠ°ΡΠ°Π΅Π²ΠΎ-Π§Π΅ΡΠΊΠ΅ΡΡΠΈΠΈ
The clinical and genetic features of hereditary motor and sensory neuropathy (HMSN; CharcotβMarieβTooth disease, CMT) causedΒ by newly identified missense mutation s.65G>T (p.Pro22His) in NEFL gene located on the chromosome 8Ρ21.2 are described. The diseaseΒ was diagnosed in a large family from Ust-Dzhegutinsky district of the Karachay-Cherkess Republic with the segregation of the diseaseΒ in four generations. The prevalence of the HMSN in that district was found to be 1:4340 persons, including 1:3376 among Karachays.Β The clinical picture of the disease was characterized by onset at the age of 11β14 years, weakness in foot muscles and steppage gait.Β The specific features in the majority of patients were the absence of major sensory disturbances, as well as long-term preserved distal armΒ muscles. Nerve conduction velocity in the median nerve varied from 30 to 42 m/s, which corresponds to values in patients with CMT2E,Β previously described.Π ΡΡΠ°ΡΡΠ΅ ΠΎΠΏΠΈΡΠ°Π½Ρ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΌΠΎΡΠΎΡΠ½ΠΎ-ΡΠ΅Π½ΡΠΎΡΠ½ΠΎΠΉ Π½Π΅ΠΉΡΠΎΠΏΠ°ΡΠΈΠΈ (ΠΠΠ‘Π, Π±ΠΎΠ»Π΅Π·Π½ΡΒ Π¨Π°ΡΠΊΠΎβΠΠ°ΡΠΈβΠ’ΡΡΠ°, ΠΠ¨ΠΠ’), ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΠΎΠΉ Π²Π½ΠΎΠ²Ρ Π²ΡΡΠ²Π»Π΅Π½Π½ΠΎΠΉ ΠΌΠΈΡΡΠ΅Π½Ρ-ΠΌΡΡΠ°ΡΠΈΠ΅ΠΉ Ρ.65G>T (p.Pro22His) Π² Π³Π΅Π½Π΅ NEFL Π½Π° Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΠ΅ 8Ρ21.2, Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΈΠ· ΡΠ΅ΠΌΡΠΈ, ΠΏΡΠΎΠΆΠΈΠ²Π°ΡΡΠ΅ΠΉ Π² Π£ΡΡΡ-ΠΠΆΠ΅Π³ΡΡΠΈΠ½ΡΠΊΠΎΠΌ ΡΠ°ΠΉΠΎΠ½Π΅ ΠΠ°ΡΠ°ΡΠ°Π΅Π²ΠΎ-Π§Π΅ΡΠΊΠ΅ΡΡΠΊΠΎΠΉ Π Π΅ΡΠΏΡΠ±Π»ΠΈΠΊΠΈ, Ρ ΡΠ΅Π³ΡΠ΅Π³Π°ΡΠΈΠ΅ΠΉΒ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ Π² 4 ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΡΡ
. Π Π°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΠΎΡΡΡ ΠΠΠ‘Π Π² ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΌ ΡΠ°ΠΉΠΎΠ½Π΅ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 1:4340 ΡΠ΅Π»ΠΎΠ²Π΅ΠΊ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ 1:3376Β ΡΡΠ΅Π΄ΠΈ ΠΊΠ°ΡΠ°ΡΠ°Π΅Π²ΡΠ΅Π². ΠΠ°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ ΠΌΠ°Π½ΠΈΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π»ΠΎ Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ 11β14 Π»Π΅Ρ Ρ ΠΏΠΎΡΠ²Π»Π΅Π½ΠΈΡ ΡΠ»Π°Π±ΠΎΡΡΠΈ ΡΡΠΎΠΏ ΠΈ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ΅ΠΏΠΏΠ°ΠΆΠ½ΠΎΠΉΒ ΠΏΠΎΡ
ΠΎΠ΄ΠΊΠΈ. ΠΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ β ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ Π·Π½Π°ΡΠΈΠΌΡΡ
ΡΠ°ΡΡΡΡΠΎΠΉΡΡΠ² ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ Ρ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π° ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΡΡ
Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΈ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½Π°Ρ ΡΠΎΡ
ΡΠ°Π½Π½ΠΎΡΡΡ ΠΌΡΡΡ Π΄ΠΈΡΡΠ°Π»ΡΠ½ΡΡ
ΠΎΡΠ΄Π΅Π»ΠΎΠ² ΡΡΠΊ. ΠΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ ΡΠΊΠΎΡΠΎΡΡΠΈ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½ΠΈΡ Π²ΠΎΠ·Π±ΡΠΆΠ΄Π΅Π½ΠΈΡ ΠΏΠΎ ΡΡΠ΅Π΄ΠΈΠ½Π½ΠΎΠΌΡ Π½Π΅ΡΠ²Ρ ΠΊΠΎΠ»Π΅Π±Π°Π»ΠΈΡΡ ΠΎΡ 30 Π΄ΠΎ 42 ΠΌ/Ρ, ΡΡΠΎ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΎΠ²Π°Π»ΠΎ ΡΠ°ΠΊΠΎΠ²ΡΠΌ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠ¨ΠΠ’ ΡΠΈΠΏΠ° 2Π, ΠΎΠΏΠΈΡΠ°Π½Π½ΡΠΌΒ ΡΠ°Π½Π΅Π΅
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
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