64 research outputs found
Modern philological knowledge: anthropocentrism and linguistic identity
The article aims at analyzing the actual status of the "linguistic persona" category in the modern linguistic studies both in Russia and abroad. It is shown that the anthropocentric paradigm dominates in modern scientific knowledg
ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠ°Ρ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ° Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΡ ΠΌΡΡΠ΅ΡΠ½ΡΡ Π΄ΠΈΡΡΡΠΎΡΠΈΠΉ (ΡΠ°ΡΡΡ 2)
Dystroglycanopathy is one of the groups of congenital muscular dystrophies, the occurrence of which is associated with a disorder of Ξ±-dystroglycan glycosylation. To date, 18 genes responsible for the development of this condition are known. The 2nd part of this review presents the classification, phenotypic forms, clinical features, pathogenesis and etiology of this type of congenital muscular dystrophies. In addition, the issues of molecular diagnosis of congenital muscular dystrophies are considered and information on modern developments in the treatment of this pathology is provided.ΠΠΈΡΡΡΠΎΠ³Π»ΠΈΠΊΠ°Π½ΠΎΠΏΠ°ΡΠΈΠΈ β ΠΎΠ΄Π½Π° ΠΈΠ· Π³ΡΡΠΏΠΏ Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΡ
ΠΌΡΡΠ΅ΡΠ½ΡΡ
Π΄ΠΈΡΡΡΠΎΡΠΈΠΉ, Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΠ΅ ΠΊΠΎΡΠΎΡΡΡ
ΡΠ²ΡΠ·Π°Π½ΠΎ Ρ Π½Π°ΡΡΡΠ΅Π½ΠΈΠ΅ΠΌ Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Ξ±-Π΄ΠΈΡΡΡΠΎΠ³Π»ΠΈΠΊΠ°Π½Π°. Π‘Π΅Π³ΠΎΠ΄Π½Ρ ΠΈΠ·Π²Π΅ΡΡΠ½ΠΎ 18 Π³Π΅Π½ΠΎΠ², ΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΡΡ
Π·Π° ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΡΡΠΎΠ³ΠΎ ΡΠΎΡΡΠΎΡΠ½ΠΈΡ. ΠΠΎ 2-ΠΉ ΡΠ°ΡΡΠΈ Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΠΎΠ±Π·ΠΎΡΠ° ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΠΊΠ»Π°ΡΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ, ΡΠ΅Π½ΠΎΡΠΈΠΏΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠΎΡΠΌΡ, ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΡΠΈΠ·Π½Π°ΠΊΠΈ, ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅Π· ΠΈ ΡΡΠΈΠΎΠ»ΠΎΠ³ΠΈΡ Π΄Π°Π½Π½ΠΎΠΉ ΡΠΎΡΠΌΡ Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΡ
ΠΌΡΡΠ΅ΡΠ½ΡΡ
Π΄ΠΈΡΡΡΠΎΡΠΈΠΉ. ΠΠΎΠΌΠΈΠΌΠΎ ΡΡΠΎΠ³ΠΎ, ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ Π²ΠΎΠΏΡΠΎΡΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΡ
ΠΌΡΡΠ΅ΡΠ½ΡΡ
Π΄ΠΈΡΡΡΠΎΡΠΈΠΉ ΠΈ ΠΏΡΠ΅Π΄ΠΎΡΡΠ°Π²Π»Π΅Π½Ρ ΡΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΎ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ°Ρ
ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π΄Π°Π½Π½ΠΎΠΉ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΈ
ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠ°Ρ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ° Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΡ ΠΌΡΡΠ΅ΡΠ½ΡΡ Π΄ΠΈΡΡΡΠΎΡΠΈΠΉ (ΡΠ°ΡΡΡ 1)
Congenital muscular dystrophy is an extremely heterogeneous group of hereditary neuromuscular diseases that are clinically characterized by muscular hypotonia, progressive muscle weakness, and dystrophic changes in the muscles. Overlapping clinical symptoms and many genes that have to be analyzed to determine the specific form of the disease in the patient make diagnosis difficult. The molecular genetic stage of diagnosis includes many different methods depending on the clinical hypothesis and their application has not lost its relevance even in the era of massive parallel sequencing. In addition to DNA sequence analysis, the analysis of muscle protein expression can also play a significant role in the diagnosis of congenital muscular dystrophy. In the review, we will consider the most important etiological, pathophysiological, clinical and laboratory data of the main forms of congenital muscular dystrophy known today.ΠΡΠΎΠΆΠ΄Π΅Π½Π½ΡΠ΅ ΠΌΡΡΠ΅ΡΠ½ΡΠ΅ Π΄ΠΈΡΡΡΠΎΡΠΈΠΈ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΡΡ ΡΠΎΠ±ΠΎΠΉ ΡΡΠ΅Π·Π²ΡΡΠ°ΠΉΠ½ΠΎ Π³Π΅ΡΠ΅ΡΠΎΠ³Π΅Π½Π½ΡΡ Π³ΡΡΠΏΠΏΡ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΡΡ
Π½Π΅ΡΠ²Π½ΠΎ-ΠΌΡΡΠ΅ΡΠ½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, ΠΊΠΎΡΠΎΡΡΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΡΡΡΡ ΠΌΡΡΠ΅ΡΠ½ΠΎΠΉ Π³ΠΈΠΏΠΎΡΠΎΠ½ΠΈΠ΅ΠΉ, ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΡΡΡΠ΅ΠΉ ΠΌΡΡΠ΅ΡΠ½ΠΎΠΉ ΡΠ»Π°Π±ΠΎΡΡΡΡ ΠΈ Π΄ΠΈΡΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡΠΌΠΈ Π² ΠΌΡΡΡΠ°Ρ
. ΠΠ΅ΡΠ΅ΠΊΡΡΠ²Π°ΡΡΠΈΠ΅ΡΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠΈΠΌΠΏΡΠΎΠΌΡ ΠΈ Π±ΠΎΠ»ΡΡΠΎΠ΅ ΡΠΈΡΠ»ΠΎ Π³Π΅Π½ΠΎΠ², ΠΊΠΎΡΠΎΡΡΠ΅ Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎ ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°ΡΡ Π΄Π»Ρ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΈΡ ΠΊΠΎΠ½ΠΊΡΠ΅ΡΠ½ΠΎΠΉ ΡΠΎΡΠΌΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°, Π·Π°ΡΡΡΠ΄Π½ΡΡΡ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΡ. ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΡΠ°ΠΏ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π²ΠΊΠ»ΡΡΠ°Π΅Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ, Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π³ΠΈΠΏΠΎΡΠ΅Π·Ρ, ΠΈ ΠΈΡ
ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π½Π΅ ΡΡΡΠ°ΡΠΈΠ»ΠΎ Π°ΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ Π΄Π°ΠΆΠ΅ Π² ΡΠΏΠΎΡ
Ρ ΠΌΠ°ΡΡΠΎΠ²ΠΎΠ³ΠΎ ΠΏΠ°ΡΠ°Π»Π»Π΅Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ. ΠΠΎΠΌΠΈΠΌΠΎ Π°Π½Π°Π»ΠΈΠ·Π° ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΠΠ Π² Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ΅ Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΡ
ΠΌΡΡΠ΅ΡΠ½ΡΡ
Π΄ΠΈΡΡΡΠΎΡΠΈΠΉ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΡΡ ΡΠΎΠ»Ρ ΡΠ°ΠΊΠΆΠ΅ ΠΌΠΎΠΆΠ΅Ρ ΠΈΠ³ΡΠ°ΡΡ Π°Π½Π°Π»ΠΈΠ· ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΌΡΡΠ΅ΡΠ½ΠΎΠ³ΠΎ Π±Π΅Π»ΠΊΠ°. Π ΠΎΠ±Π·ΠΎΡΠ΅ ΠΌΡ ΡΠ°ΡΡΠΌΠΎΡΡΠΈΠΌ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ Π²Π°ΠΆΠ½ΡΠ΅ ΡΡΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅, ΠΏΠ°ΡΠΎΡΠΈΠ·ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅, ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
ΡΠΎΡΠΌ Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΡ
ΠΌΡΡΠ΅ΡΠ½ΡΡ
Π΄ΠΈΡΡΡΠΎΡΠΈΠΉ, ΠΈΠ·Π²Π΅ΡΡΠ½ΡΡ
Π½Π° ΡΠ΅Π³ΠΎΠ΄Π½ΡΡΠ½ΠΈΠΉ Π΄Π΅Π½Ρ
ΠΠΈΠΎΠΏΠ°ΡΠΈΡ ΠΠΈΠΎΡΠΈ: Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ° ΡΠ΅ΠΌΠ΅ΠΈΜΠ½ΠΎΠ³ΠΎ ΡΠ»ΡΡΠ°Ρ Π΄ΠΈΡΡΠ΅ΡΠ»ΠΈΠ½ΠΎΠΏΠ°ΡΠΈΠΈ
Miyoshi myopathy (MM) is a rare distal form of limb-girdle muscular dystrophies characterized by weakness primarily affecting the calves in adolescence or young adulthood, with slow progression, the ascending pattern of involvement of muscle groups in an atrophic process, and with obvious clinical polymorphism at onset (3 allelic variants are described). In MM, hypercreatine phosphatemia is noted to be 20β 50 times the normal blood concentrations. MM is referred to the dysferlinopathies with different mutations in the DYSF gene.Β In that manuscript we describe a 20-year familial case of 2 brothers with MM, including changes in their clinical manifestations, biochemical, CT and EMG parameters. The diagnosis was verified by whole exome sequencing of the DYSF gene to identify a homozygous missense mutations (c. 5302C>T) leading to replacement in the polypeptide chain of DYSF p.Arg1768Trp. The differential diagnosis of MM with clinically similar hereditary neuromuscular diseases is discussed.Β ΠΠΈΠΎΠΏΠ°ΡΠΈΡ ΠΠΈΠΎΡΠΈ (ΠΠ) β ΠΎΠ΄Π½Π° ΠΈΠ· ΡΠ΅Π΄ΠΊΠΈΡ
Π΄ΠΈΡΡΠ°Π»ΡΠ½ΡΡ
ΡΠΎΡΠΌ ΠΏΠΎΡΡΠ½ΠΎ-ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ½ΡΡ
ΠΌΡΡΠ΅ΡΠ½ΡΡ
Π΄ΠΈΡΡΡΠΎΡΠΈΠΈΜ, Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΠ΅ΡΡΡ ΡΠ»Π°Π±ΠΎΡΡΡΡ, ΠΏΠ΅ΡΠ²ΠΎΠ½Π°ΡΠ°Π»ΡΠ½ΠΎ Π·Π°ΡΡΠ°Π³ΠΈΠ²Π°ΡΡΠ΅ΠΈΜ ΠΈΠΊΡΠΎΠ½ΠΎΠΆΠ½ΡΠ΅ ΠΌΡΡΡΡ Π² ΠΏΠΎΠ΄ΡΠΎΡΡΠΊΠΎΠ²ΠΎΠΌ ΠΈΠ»ΠΈ ΡΠ°Π½Π½Π΅ΠΌ Π²Π·ΡΠΎΡΠ»ΠΎΠΌ Π²ΠΎΠ·ΡΠ°ΡΡΠ΅, ΠΌΠ΅Π΄Π»Π΅Π½Π½ΠΎ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΡΡΡΠΈΠΌ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ΠΌ, Β«Π²ΠΎΡΡ
ΠΎΠ΄ΡΡΠΈΠΌΒ» ΠΏΠ°ΡΡΠ΅ΡΠ½ΠΎΠΌ Π²ΠΎΠ²Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΌΡΡΠ΅ΡΠ½ΡΡ
Π³ΡΡΠΏΠΏ Π² Π°ΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠΈΜ ΠΏΡΠΎΡΠ΅ΡΡ, Ρ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΌ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠΎΠΌ Π² Π΄Π΅Π±ΡΡΠ½ΠΎΠΈΜ ΡΡΠ°Π΄ΠΈΠΈ (ΠΎΠΏΠΈΡΠ°Π½Ρ 3 Π°Π»Π»Π΅Π»ΡΠ½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠ°). ΠΡΠΈ ΠΠ ΠΎΡΠΌΠ΅ΡΠ°Π΅ΡΡΡ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½Π°Ρ Π³ΠΈΠΏΠ΅ΡΠΊΡΠ΅Π°ΡΠΈΠ½ΡΠΎΡΡΠ°ΡΠ΅ΠΌΠΈΡ, ΠΏΡΠ΅Π²ΡΡΠ°ΡΡΠ°Ρ Π½ΠΎΡΠΌΡ Π² 20β50 ΡΠ°Π·. ΠΠ ΠΎΡΠ½ΠΎΡΠΈΡΡΡ ΠΊ Π΄ΠΈΡΡΠ΅ΡΠ»ΠΈΠ½ΠΎΠΏΠ°ΡΠΈΡΠΌ Ρ ΡΠ°Π·Π½ΠΎΠΎΠ±ΡΠ°Π·Π½ΡΠΌΠΈ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ DYSF.Β ΠΡ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΠΌ 20-Π»Π΅ΡΠ½Π΅Π΅ ΡΠ΅ΠΌΠ΅ΠΈΜΠ½ΠΎΠ΅ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΠ΅ 2 Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΠ Π±ΡΠ°ΡΡΠ΅Π² Ρ ΠΎΠΏΠΈΡΠ°Π½ΠΈΠ΅ΠΌ Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΈΜ, Π±ΠΈΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
, ΠΊΠΎΠΌΠΏΡΡΡΠ΅ΡΠ½ΠΎ-ΡΠΎΠΌΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈ ΡΠ»Π΅ΠΊΡΡΠΎΠΌΠΈΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΠΎΠ². ΠΠΈΠ°Π³Π½ΠΎΠ· Π±ΡΠ» Π²Π΅ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΠΎΠ»Π½ΠΎΡΠΊΠ·ΠΎΠΌΠ½ΠΎΠ³ΠΎ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½Π° DYSF Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΠ΅ΠΌ ΠΌΠΈΡΡΠ΅Π½Ρ-ΠΌΡΡΠ°ΡΠΈΠΈ Π² Ρ.5302 (Π‘>T) Π² Π³ΠΎΠΌΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΠΎΠΌ ΡΠΎΡΡΠΎΡΠ½ΠΈΠΈ, ΠΏΡΠΈΠ²Π΅Π΄ΡΠ΅ΠΈΜ ΠΊ Π·Π°ΠΌΠ΅Π½Π΅ Π² ΠΏΠΎΠ»ΠΈΠΏΠ΅ΠΏΡΠΈΠ΄Π½ΠΎΠΈΜ ΡΠ΅ΠΏΠΎΡΠΊΠ΅ DYSF Ρ.Arg1768Trp. ΠΠ±ΡΡΠΆΠ΄Π°Π΅ΡΡΡ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½Π°Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ° ΠΠ ΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈ ΡΡ
ΠΎΠ΄Π½ΡΡ
Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΡΡ
Π½Π΅ΡΠ²Π½ΠΎ-ΠΌΡΡΠ΅ΡΠ½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΈΜ.
Π‘ΠΈΠ½Π΄ΡΠΎΠΌ ΠΠΉΠΌΠ΅βΠΡΠΈΠΏΠΏ Ρ ΡΠΎΡΡΠΈΠΉΡΠΊΠΎΠ³ΠΎ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° Ρ Π²Π½ΠΎΠ²Ρ Π²ΡΡΠ²Π»Π΅Π½Π½ΠΎΠΉ ΠΌΡΡΠ°ΡΠΈΠ΅ΠΉ Π² Π³Π΅Π½Π΅ MAF
AymΓ©βGripp syndrome is a rare autosomal dominant syndrome caused by mutations in the MAF gene and is characterized by a pronounced phenotypic polymorphism. The core of clinical signs consists of congenital cataracts, sensorineural hearing loss, specific dysmorphic facial features and intellectual disabilities. With varying frequency, patients have: radioulnar synostosis, ArnoldβChiari malformation, aseptic pericarditis, dental anomaly and osteoarthritis. The article presents the clinical and genetic characteristics of the first Russian patient with AymΓ©βGripp syndrome caused by a newly identified mutation s.173C>A (p.Thr58Asn NM_005360.4) in a heterozygous state in the MAF gene. The influence of the loΒ calization and type of amino acid substitutions in the protein product of the gene on the severity and specificity of the clinical manifestations of the syndrome is discussed.Β Π‘ΠΈΠ½Π΄ΡΠΎΠΌ ΠΠΉΠΌΠ΅βΠΡΠΈΠΏΠΏ β ΡΠ΅Π΄ΠΊΠΎΠ΅ Π°ΡΡΠΎΡΠΎΠΌΠ½ΠΎ-Π΄ΠΎΠΌΠΈΠ½Π°Π½ΡΠ½ΠΎΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΠΎΠ΅ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ MAF, ΠΊΠΎΡΠΎΡΠΎΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΠ΅ΡΡΡ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΌ ΡΠ΅Π½ΠΎΡΠΈΠΏΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠΎΠΌ. Π―Π΄ΡΠΎ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΈΠ·Π½Π°ΠΊΠΎΠ² ΡΠΎΡΡΠΎΠΈΡ ΠΈΠ· Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΠΎΠΉ ΠΊΠ°ΡΠ°ΡΠ°ΠΊΡΡ, Π½Π΅ΠΉΡΠΎΡΠ΅Π½ΡΠΎΡΠ½ΠΎΠΉ ΡΡΠ³ΠΎΡΡ
ΠΎΡΡΠΈ, ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π΄ΠΈΠ·ΠΌΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ΅ΡΡ ΡΡΡΠΎΠ΅Π½ΠΈΡ Π»ΠΈΡΠ° ΠΈ ΠΈΠ½ΡΠ΅Π»Π»Π΅ΠΊΡΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ Π΄Π΅ΡΠΈΡΠΈΡΠ°. Π‘ ΡΠ°Π·Π»ΠΈΡΠ½ΠΎΠΉ ΡΠ°ΡΡΠΎΡΠΎΠΉ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΎΡΠΌΠ΅ΡΠ°ΡΡΡΡ ΡΠ°Π΄ΠΈΠΎΡΠ»ΡΠ½Π°ΡΠ½ΡΠΉ ΡΠΈΠ½ΠΎΡΡΠΎΠ·, Π°Π½ΠΎΠΌΠ°Π»ΠΈΡ ΠΡΠ½ΠΎΠ»ΡΠ΄Π°β ΠΠΈΠ°ΡΠΈ, Π°ΡΠ΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΏΠ΅ΡΠΈΠΊΠ°ΡΠ΄ΠΈΡ, Π°Π½ΠΎΠΌΠ°Π»ΠΈΡ Π·ΡΠ±ΠΎΠ² ΠΈ ΠΎΡΡΠ΅ΠΎΠ°ΡΡΡΠΈΡΡ. ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΠΏΠ΅ΡΠ²ΠΎΠΉ ΡΠΎΡΡΠΈΠΉΡΠΊΠΎΠΉ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΊΠΈ Ρ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ ΠΠΉΠΌΠ΅βΠΡΠΈΠΏΠΏ, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΠΌ Π²Π½ΠΎΠ²Ρ Π²ΡΡΠ²Π»Π΅Π½Π½ΠΎΠΉ ΠΌΡΡΠ°ΡΠΈΠ΅ΠΉ Ρ.173Π‘>Π (p.Thr58Asn NM_005360.4) Π² Π³Π΅ΡΠ΅ΡΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΠΎΠΌ ΡΠΎΡΡΠΎΡΠ½ΠΈΠΈ Π² Π³Π΅Π½Π΅ MAF. ΠΠ±ΡΡΠΆΠ΄Π°Π΅ΡΡΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΈ ΡΠΈΠΏΠ° Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡΠ½ΡΡ
Π·Π°ΠΌΠ΅Π½ Π² Π±Π΅Π»ΠΊΠΎΠ²ΠΎΠΌ ΠΏΡΠΎΠ΄ΡΠΊΡΠ΅ Π³Π΅Π½Π° Π½Π° ΡΡΠΆΠ΅ΡΡΡ ΠΈ ΡΠΏΠ΅ΡΠΈΡΠΈΠΊΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ°.
Influence of human peripheral blood samples preprocessing on the quality of Hi-C libraries
The genome-wide variant of the chromatin conformation capture technique (Hi-C) is a powerful tool for revealing patterns of genome spatial organization, as well as for understanding the effects of their disturbance on disease development. In addition, Hi-C can be used to detect chromosomal rearrangements, including balanced translocations and inversions. The use of the Hi-C method for the detection of chromosomal rearrangements is becoming more widespread. Modern high-throughput methods of genome analysis can effectively reveal point mutations and unbalanced chromosomal rearrangements. However, their sensitivity for determining translocations and inversions remains rather low. The storage of whole blood samples can affect the amount and integrity of genomic DNA, and it can distort the results of subsequent analyses if the storage was not under proper conditions. The Hi-C method is extremely demanding on the input material. The necessary condition for successfully applying Hi-C and obtaining high-quality data is the preservation of the spatial chromatin organization within the nucleus. The purpose of this study was to determine the optimal storage conditions of blood samples for subsequent Hi-C analysis. We selected 10 different conditions for blood storage and sample processing. For each condition, we prepared and sequenced Hi-C libraries. The quality of the obtained data was compared. As a result of the work, we formulated the requirements for the storage and processing of samples to obtain high-quality Hi-C data. We have established the minimum volume of blood sufficient for conducting Hi-C analysis. In addition, we have identified the most suitable methods for isolation of peripheral blood mononuclear cells and their long-term storage. The main requirement we have formulated is not to freeze whole blood
Π‘ΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ ΡΠ΅Π½ΠΎΡΠΈΠΏΠΎΠ² ΠΏΠΎΡΡΠ½ΠΎ- ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ½ΡΡ ΠΌΡΡΠ΅ΡΠ½ΡΡ Π΄ΠΈΡΡΡΠΎΡΠΈΠΉ 2Π ΠΈ 2I ΡΠΈΠΏΠΎΠ²
A comparative analysis of the frequency of occurrence of 36 clinical symptoms in the three groups of patients with LGMD 2A and LGMD 2Itypes and LGMD those patients who have mutations in CAPN3 and FKRP was detected. The absence of a particular symptom, allowing for thedifferentiation of these genetic variants on clinical level.Β An algorithm for molecular genetic investigation of patients according to age at onset and some clinical symptoms. The proposed algorithm canΒ significantly reduce the economic and time costs during expensive standing DNA analysis.ΠΡΠΎΠ²Π΅Π΄Π΅Π½ ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΡΠ°ΡΡΠΎΡΡ Π²ΡΡΡΠ΅ΡΠ°Π΅ΠΌΠΎΡΡΠΈ 36 ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠΈΠΌΠΏΡΠΎΠΌΠΎΠ² Π² 3 Π³ΡΡΠΏΠΏΠ°Ρ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ²: Ρ ΠΏΠΎΡΡΠ½ΠΎ-ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ½ΠΎΠΉΒ ΠΌΡΡΠ΅ΡΠ½ΠΎΠΉ Π΄ΠΈΡΡΡΠΎΡΠΈΠ΅ΠΉ (ΠΠΠΠ) 2Π ΠΈ 2I ΡΠΈΠΏΠΎΠ² ΠΈ Ρ ΠΠΠΠ, ΠΏΡΠΈ ΠΊΠΎΡΠΎΡΠΎΠΉ ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π³Π΅Π½Π°Ρ
CAPN3 ΠΈ FKRP Π½Π΅ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎΒ ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΈΠΌΠΏΡΠΎΠΌΠΎΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ°, ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡΠ΅Π³ΠΎ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΡΡ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°ΡΠΈΡ ΡΡΠΈΡ
Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² ΡΠΎΠ»ΡΠΊΠΎΒ Π½Π° ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΌ ΡΡΠΎΠ²Π½Π΅.Β ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½ Π°Π»Π³ΠΎΡΠΈΡΠΌ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π±ΠΎΠ»ΡΠ½ΡΡ
Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ Π²ΠΎΠ·ΡΠ°ΡΡΠ° Π΄Π΅Π±ΡΡΠ° Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠΈΠΌΠΏΡΠΎΠΌΠΎΠ². ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π½ΡΠΉ Π°Π»Π³ΠΎΡΠΈΡΠΌ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΡ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΡΠ½ΠΈΠ·ΠΈΡΡ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ Π²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅Β Π·Π°ΡΡΠ°ΡΡ ΠΏΡΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ Π΄ΠΎΡΠΎΠ³ΠΎΡΡΠΎΡΡΠΈΡ
ΠΠΠ-Π°Π½Π°Π»ΠΈΠ·ΠΎΠ²
ΠΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΠΏΠ΅ΠΊΡΡΠ° Π²ΡΡΠ²Π»Π΅Π½Π½ΡΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ DMD Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΠΌΠ΅ΡΠΎΠ΄ΠΈΡΠ΅ΡΠΊΠΈΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠ΅ΠΉ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΠΈ
Background. Duchenne muscular dystrophy (DMD) is a severe, progressive form of muscular dystrophy that occurs in children between one and three years of age. The disease is mainly characterized by weakness of the proximal muscles, which leads to difficulty in movement, and ultimately to complete disability. Becker muscular dystrophy (BMD) is a milder allelic form of the disorder characterized by late onset and slow progression. The cause of the development of DMD/BMD is mutations in the DMD gene, leading to a deficiency in the production of various isoforms of the dystrophin protein family. The most common mutations in case of DMD/BMD are gross deletions (55β65 %) and duplications (6β11 %) of one or several exons The remaining cases of DMD/BMD are due to small mutations (approximately 20β30 %). Depending on the methodological capabilities of the laboratory, the idea of the spectrum of mutations in the DMD gene changed, which is important in genetic counseling of patients and planning the therapy available today.Aim. To analyze the spectrum of mutations in the DMD gene, including three time slices, depending on the methodological capabilities of the laboratory.Materials and methods. We analyzed the spectrum of mutations in the DMD gene for a sample of 2957 patients admitted to the laboratory of DNA diagnostics of the Research Centre for Medical Genetics with a referral diagnosis of DMD/BMD. Depending on the time of treatment and the capabilities of the laboratory, patients were divided into three groups: 2008β2015, 2016β2018, 2019β2022.Results. As a result of the study, the full range of mutations in the DMD gene was analyzed over three-time intervals, which makes it possible to get an idea of the distribution of mutation types in the sample among Russian patients. Regardless of the methodological capabilities of the laboratory, the spectrum of mutations in the DMD gene remains biased relative to world data. At the moment, there is a significant decrease in the proportion of extended deletions (50.7β59.6 %), while the proportion of extended duplications (11.8β17.2 %) and small mutations (23.2β35.0 %) increased. We assume that the main reason for such features of the spectrum is ethnic and population differences.Conclusion. Duchenne/Becker muscular dystrophy (DMD/BMD) is the most common form of muscular dystrophy, accounting for more than 50 % of all cases. Determination of the spectrum of mutations provides an understanding of their frequencies, which in the future may help patients in the appointment of therapy specific to a particular type of mutation.Β ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΡΡΠ΅ΡΠ½Π°Ρ Π΄ΠΈΡΡΡΠΎΡΠΈΡ ΠΡΡΠ΅Π½Π½Π° (ΠΠΠ) β ΡΡΠΆΠ΅Π»Π°Ρ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΡΡΡΠ°Ρ ΡΠΎΡΠΌΠ° ΠΌΡΡΠ΅ΡΠ½ΡΡ
Π΄ΠΈΡΡΡΠΎΡΠΈΠΉ, ΠΏΡΠΎΡΠ²Π»ΡΡΡΠ°ΡΡΡ Ρ Π΄Π΅ΡΠ΅ΠΉ Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ ΠΎΡ 1 Π΄ΠΎ 3 Π»Π΅Ρ. ΠΠ°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ Π² ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΌ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΠ΅ΡΡΡ ΡΠ»Π°Π±ΠΎΡΡΡΡ ΠΏΡΠΎΠΊΡΠΈΠΌΠ°Π»ΡΠ½ΡΡ
ΠΌΡΡΡ, ΡΡΠΎ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ Π·Π°ΡΡΡΠ΄Π½Π΅Π½ΠΈΡΠΌ ΠΏΡΠΈ Π΄Π²ΠΈΠΆΠ΅Π½ΠΈΠΈ ΠΈ Π² ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΠΌ ΠΈΡΠΎΠ³Π΅ ΠΊ ΠΏΠΎΠ»Π½ΠΎΠΉ ΠΈΠ½Π²Π°Π»ΠΈΠ΄ΠΈΠ·Π°ΡΠΈΠΈ. ΠΡΡΠ΅ΡΠ½Π°Ρ Π΄ΠΈΡΡΡΠΎΡΠΈΡ ΠΠ΅ΠΊΠΊΠ΅ΡΠ° (ΠΠΠ) β Π±ΠΎΠ»Π΅Π΅ ΠΌΡΠ³ΠΊΠ°Ρ Π°Π»Π»Π΅Π»ΡΠ½Π°Ρ ΡΠΎΡΠΌΠ° Π±ΠΎΠ»Π΅Π·Π½ΠΈ, Π΄Π»Ρ ΠΊΠΎΡΠΎΡΠΎΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ½Ρ ΠΏΠΎΠ·Π΄Π½ΡΡ ΠΌΠ°Π½ΠΈΡΠ΅ΡΡΠ°ΡΠΈΡ ΠΈ ΠΌΠ΅Π΄Π»Π΅Π½Π½ΠΎΠ΅ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅. ΠΡΠΈΡΠΈΠ½ΠΎΠΉ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΠΠ/ΠΠΠ ΡΠ»ΡΠΆΠ°Ρ ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π³Π΅Π½Π΅ DMD, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠΈΠ΅ ΠΊ Π΄Π΅ΡΠΈΡΠΈΡΡ ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΈΠ·ΠΎΡΠΎΡΠΌ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° Π±Π΅Π»ΠΊΠ° Π΄ΠΈΡΡΡΠΎΡΠΈΠ½Π°. Π‘Π°ΠΌΡΠΌΠΈ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΡΠΌΠΈ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ ΠΏΡΠΈ ΠΠΠ/ΠΠΠ ΡΠ²Π»ΡΡΡΡΡ ΠΏΡΠΎΡΡΠΆΠ΅Π½Π½ΡΠ΅ Π΄Π΅Π»Π΅ΡΠΈΠΈ (55β65 %) ΠΈ Π΄ΡΠΏΠ»ΠΈΠΊΠ°ΡΠΈΠΈ (6β11 %) ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΈΠ»ΠΈ Π½Π΅ΡΠΊΠΎΠ»ΡΠΊΠΈΡ
ΡΠΊΠ·ΠΎΠ½ΠΎΠ². ΠΡΡΠ°Π»ΡΠ½ΡΠ΅ ΡΠ»ΡΡΠ°ΠΈ ΠΠΠ/ΠΠΠ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Ρ ΡΠΎΡΠ΅ΡΠ½ΡΠΌΠΈ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ (Π΄ΠΎ 20β30 %). Π Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΠΌΠ΅ΡΠΎΠ΄ΠΈΡΠ΅ΡΠΊΠΈΡ
Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠ΅ΠΉ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΠΈ ΠΌΠ΅Π½ΡΠ»ΠΎΡΡ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ ΠΎ ΡΠΏΠ΅ΠΊΡΡΠ΅ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ DMD, ΡΡΠΎ ΠΈΠΌΠ΅Π΅Ρ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ ΠΏΡΠΈ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΠΊΠΎΠ½ΡΡΠ»ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΈ ΠΏΠ»Π°Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ Π΄ΠΎΡΡΡΠΏΠ½ΠΎΠΉ Π² Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β Π°Π½Π°Π»ΠΈΠ· ΡΠΏΠ΅ΠΊΡΡΠ° ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ DMD, Π²ΠΊΠ»ΡΡΠ°ΡΡΠΈΠΉ 3 Π²ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
ΠΎΡΡΠ΅Π·ΠΊΠ°, Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΠΌΠ΅ΡΠΎΠ΄ΠΈΡΠ΅ΡΠΊΠΈΡ
Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠ΅ΠΉ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΠΈ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½ ΡΠΏΠ΅ΠΊΡΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ DMD Π΄Π»Ρ Π²ΡΠ±ΠΎΡΠΊΠΈ ΠΈΠ· 2957 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΡΡ
Π² Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΠΈ ΠΠΠ-Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π€ΠΠΠΠ£ Β«ΠΠ΅Π΄ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π½Π°ΡΡΠ½ΡΠΉ ΡΠ΅Π½ΡΡ ΠΈΠΌ. Π°ΠΊΠ°Π΄. Π.Π. ΠΠΎΡΠΊΠΎΠ²Π°Β» Ρ Π½Π°ΠΏΡΠ°Π²Π»ΡΡΡΠΈΠΌ Π΄ΠΈΠ°Π³Π½ΠΎΠ·ΠΎΠΌ ΠΠΠ/ΠΠΠ. Π Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΠΎΠ±ΡΠ°ΡΠ΅Π½ΠΈΡ ΠΈ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠ΅ΠΉ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΡ Π±ΡΠ»ΠΈ ΡΠ°Π·Π΄Π΅Π»Π΅Π½Ρ Π½Π° 3 Π³ΡΡΠΏΠΏΡ: 2008β2015, 2016β2018 ΠΈ 2019β2022 Π³Π³.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½ΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½ ΠΏΠΎΠ»Π½ΡΠΉ ΡΠΏΠ΅ΠΊΡΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ DMD Π·Π° 3 Π²ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
ΠΎΡΡΠ΅Π·ΠΊΠ°, ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡΠΈΠΉ ΠΏΠΎΠ»ΡΡΠΈΡΡ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ ΠΎ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠΈ ΡΠΈΠΏΠΎΠ² ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π²ΡΠ±ΠΎΡΠΊΠ΅ ΡΡΠ΅Π΄ΠΈ ΡΠΎΡΡΠΈΠΉΡΠΊΠΈΡ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ². ΠΠ΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎ ΠΎΡ ΠΌΠ΅ΡΠΎΠ΄ΠΈΡΠ΅ΡΠΊΠΈΡ
Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠ΅ΠΉ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΠΈ Π² ΡΠ°Π·Π½ΡΠ΅ Π²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ ΠΏΠ΅ΡΠΈΠΎΠ΄Ρ ΡΠΏΠ΅ΠΊΡΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ DMD ΠΎΡΡΠ°Π΅ΡΡΡ ΡΠΌΠ΅ΡΠ΅Π½Π½ΡΠΌ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΠΌΠΈΡΠΎΠ²ΡΡ
Π΄Π°Π½Π½ΡΡ
. Π Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ Π½Π°Π±Π»ΡΠ΄Π°Π΅ΡΡΡ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ Π΄ΠΎΠ»ΠΈ ΠΏΡΠΎΡΡΠΆΠ΅Π½Π½ΡΡ
Π΄Π΅Π»Π΅ΡΠΈΠΉ (50,7β59,6 %), Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ Π΄ΠΎΠ»ΠΈ ΠΏΡΠΎΡΡΠΆΠ΅Π½Π½ΡΡ
Π΄ΡΠΏΠ»ΠΈΠΊΠ°ΡΠΈΠΉ (11,8β17,2 %) ΠΈ ΡΠΎΡΠ΅ΡΠ½ΡΡ
ΠΌΡΡΠ°ΡΠΈΠΉ (23,2β35,0 %) ΡΠ²Π΅Π»ΠΈΡΠ΅Π½Ρ. ΠΡΠ½ΠΎΠ²Π½ΠΎΠΉ ΠΏΡΠΈΡΠΈΠ½ΠΎΠΉ ΡΠ°ΠΊΠΈΡ
ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ ΡΠΏΠ΅ΠΊΡΡΠ°, ΠΌΡ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°Π΅ΠΌ, ΡΠ²Π»ΡΡΡΡΡ ΡΡΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ ΠΏΠΎΠΏΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΠ΅ ΡΠ°Π·Π»ΠΈΡΠΈΡ.ΠΡΠ²ΠΎΠ΄Ρ. ΠΠΠ/ΠΠΠ β Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠ°ΡΡΡΠ΅ ΡΠΎΡΠΌΡ ΠΌΡΡΠ΅ΡΠ½ΡΡ
Π΄ΠΈΡΡΡΠΎΡΠΈΠΉ, Π½Π° ΠΊΠΎΡΠΎΡΡΠ΅ ΠΏΡΠΈΡ
ΠΎΠ΄ΠΈΡΡΡ Π±ΠΎΠ»Π΅Π΅ 50 % Π²ΡΠ΅Ρ
ΡΠ»ΡΡΠ°Π΅Π². ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠΏΠ΅ΠΊΡΡΠ° ΠΌΡΡΠ°ΡΠΈΠΉ Π΄Π°Π΅Ρ ΠΏΠΎΠ½ΠΈΠΌΠ°Π½ΠΈΠ΅ ΠΎΠ± ΠΈΡ
ΡΠ°ΡΡΠΎΡΠ°Ρ
, ΡΡΠΎ Π² Π±ΡΠ΄ΡΡΠ΅ΠΌ ΠΌΠΎΠΆΠ΅Ρ ΠΏΠΎΠΌΠΎΡΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°ΠΌ Π² Π½Π°Π·Π½Π°ΡΠ΅Π½ΠΈΠΈ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ, ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΠΉ Π΄Π»Ρ ΠΊΠΎΠ½ΠΊΡΠ΅ΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠΏΠ° ΠΌΡΡΠ°ΡΠΈΠΉ.
ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΠΊΠΎΠ½ΡΡΠ°ΠΊΡΡΡ ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΈ Π»ΠΈΡΠ°, Π³ΠΈΠΏΠΎΡΠΎΠ½ΠΈΠΈ ΠΈ Π·Π°Π΄Π΅ΡΠΆΠΊΠΈ ΠΏΡΠΈΡ ΠΎΠΌΠΎΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ (OMIM:616 266), ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΠΎΠ³ΠΎ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ NALCN
A description of the clinical and genetic characteristics of the syndrome of congenital contractures of the limbs and face in combination with muscular hypotonia and psychomotor retardation of 2 patients from Russia is presented. As a result of full-exome DNA sequencing, 2 heterozygous missense mutations c 4355T C and c.3541C G were found in the NALCN gene, leading to amino acid substitutions at the functionally important center of the protein molecule. The effect of identified mutations in the NALCN gene on the function of its protein and approaches to the differential diagnosis of congenital contracture syndrome of the extremities and face in combination with muscular hypotonia and psychomotor retardation with monogenic variants of distal arthrogryposis with autosomal dominant type of inheritance are discussed.ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΎ ΠΎΠΏΠΈΡΠ°Π½ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΡ
ΠΊΠΎΠ½ΡΡΠ°ΠΊΡΡΡ ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΈ Π»ΠΈΡΠ° Π² ΡΠΎΡΠ΅ΡΠ°Π½ΠΈΠΈ Ρ ΠΌΡΡΠ΅ΡΠ½ΠΎΠΉ Π³ΠΈΠΏΠΎΡΠΎΠ½ΠΈΠ΅ΠΉ ΠΈ Π·Π°Π΄Π΅ΡΠΆΠΊΠΎΠΉ ΠΏΡΠΈΡ
ΠΎΠΌΠΎΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ 2 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΈΠ· Π ΠΎΡΡΠΈΠΈ. Π ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΏΠΎΠ»Π½ΠΎΡΠΊΠ·ΠΎΠΌΠ½ΠΎΠ³ΠΎ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΠΠ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Ρ 2 Π³Π΅ΡΠ΅ΡΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΡΠ΅ ΠΌΠΈΡΡΠ΅Π½Ρ-ΠΌΡΡΠ°ΡΠΈΠΈ c.4355T>C ΠΈ c.3541C>G Π² Π³Π΅Π½Π΅ NALCN, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠΈΠ΅ ΠΊ Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡΠ½ΡΠΌ Π·Π°ΠΌΠ΅Π½Π°ΠΌ Π² ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎ Π·Π½Π°ΡΠΈΠΌΠΎΠΌ ΡΠ΅Π½ΡΡΠ΅ Π±Π΅Π»ΠΊΠΎΠ²ΠΎΠΉ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Ρ. ΠΠ±ΡΡΠΆΠ΄Π°Π΅ΡΡΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΡ
ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ NALCN Π½Π° ΡΡΠ½ΠΊΡΠΈΡ Π΅Π³ΠΎ Π±Π΅Π»ΠΊΠ° ΠΈ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Ρ ΠΊ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ΅ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΡ
ΠΊΠΎΠ½ΡΡΠ°ΠΊΡΡΡ ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΈ Π»ΠΈΡΠ° Π² ΡΠΎΡΠ΅ΡΠ°Π½ΠΈΠΈ Ρ ΠΌΡΡΠ΅ΡΠ½ΠΎΠΉ Π³ΠΈΠΏΠΎΡΠΎΠ½ΠΈΠ΅ΠΉ ΠΈ Π·Π°Π΄Π΅ΡΠΆΠΊΠΎΠΉ ΠΏΡΠΈΡ
ΠΎΠΌΠΎΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ Ρ ΠΌΠΎΠ½ΠΎΠ³Π΅Π½Π½ΡΠΌΠΈ Π²Π°ΡΠΈΠ°Π½ΡΠ°ΠΌΠΈ Π΄ΠΈΡΡΠ°Π»ΡΠ½ΡΡ
Π°ΡΡΡΠΎΠ³ΡΠΈΠΏΠΎΠ·ΠΎΠ² Ρ Π°ΡΡΠΎΡΠΎΠΌΠ½ΠΎ-Π΄ΠΎΠΌΠΈΠ½Π°Π½ΡΠ½ΡΠΌ ΡΠΈΠΏΠΎΠΌ Π½Π°ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ
POLR3A-Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π½Π°Ρ Π³ΠΈΠΏΠΎΠΌΠΈΠ΅Π»ΠΈΠ½ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½Π°Ρ Π»Π΅ΠΉΠΊΠΎΠ΄ΠΈΡΡΡΠΎΡΠΈΡ: ΠΎΠΏΠΈΡΠ°Π½ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ»ΡΡΠ°Ρ ΠΈ ΠΎΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ
Hypomyelinating leukodystrophies (HL) is a group of genetically heterogeneous neurodegenerative disorders characterized by a lack of brain myelin deposition. One of the most common autosomal recessive HL is HL type 7 caused by mutations in the POLR3A gene. We reported the first clinical case of a Russian patient with HL type 7.Proband is a 7βyearβold patient with HL type 7. The diagnosis was confirmed by genealogy, neurological examination, brain magnetic resonance imaging and molecular genetic testing. Two compoundβheterozygous variants in the POLR3A gene were revealed in the patient. Each variant was described earlier in patients with variable clinical manifestations of neurodegenerative diseases. The peculiarities of clinical manifestations in our patient were the manifestation of the disease in the first year of life, the predominance of cerebellar symptoms, a movement limitation of the jaw, leading to worsening of dysarthria, a delay in the formation of permanent teeth and short stature. The course of the disease was moderate that could be explained by different effect of the variants in the POLR3A gene.POLR3Aβrelated disease is a group of clinically heterogeneous disorders manifesting from early childhood to adulthood and characterized by isolated spastic ataxia or ataxia combined with oligodontia and hypogonadotropic hypogonadism, isolated or complicated spastic paraplegia, as well as a combination of ataxia with extrapyramidal symptoms. Our case report demonstrates the complexity of diagnostic process in the absence of a peculiar clinical picture and specific changes in brain imaging.ΠΠΈΠΏΠΎΠΌΠΈΠ΅Π»ΠΈΠ½ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ Π»Π΅ΠΉΠΊΠΎΠ΄ΠΈΡΡΡΠΎΡΠΈΠΈ (ΠΠ) β Π³ΡΡΠΏΠΏΠ° Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈ Π³Π΅ΡΠ΅ΡΠΎΠ³Π΅Π½Π½ΡΡ
Π½Π΅ΠΉΡΠΎΠ΄Π΅Π³Π΅Π½Π΅ΡΠ°ΡΠΈΠ²Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°ΡΡΠΈΡ
ΡΡ Π½Π°ΡΡΡΠ΅Π½ΠΈΠ΅ΠΌ ΠΌΠΈΠ΅Π»ΠΈΠ½ΠΈΠ·Π°ΡΠΈΠΈ. ΠΠ΄Π½ΠΎΠΉ ΠΈΠ· Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΡΡ
Π°ΡΡΠΎΡΠΎΠΌΠ½ΠΎβΡΠ΅ΡΠ΅ΡΡΠΈΠ²Π½ΡΡ
ΠΠ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΠ 7βΠ³ΠΎ ΡΠΈΠΏΠ°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½Π°Ρ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ POLR3Π.Π¦Π΅Π»ΡΡ ΡΠ°Π±ΠΎΡΡ ΡΠ²ΠΈΠ»ΠΎΡΡ ΠΏΠ΅ΡΠ²ΠΎΠ΅ ΠΎΠΏΠΈΡΠ°Π½ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎβΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊ ΡΠΎΡΡΠΈΠΉΡΠΊΠΎΠ³ΠΎ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° Ρ ΠΠ 7βΠ³ΠΎ ΡΠΈΠΏΠ° ΠΈ ΠΎΠ±Π·ΠΎΡ ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Π½ΡΡ
Π΄Π°Π½Π½ΡΡ
.ΠΡΠΎΠ±Π°Π½Π΄ β ΡΠ΅Π±Π΅Π½ΠΎΠΊ 7 Π»Π΅Ρ Ρ ΠΠ 7βΠ³ΠΎ ΡΠΈΠΏΠ°. ΠΠΈΠ°Π³Π½ΠΎΠ· ΡΡΡΠ°Π½Π°Π²Π»ΠΈΠ²Π°Π»ΡΡ Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ Π΄Π°Π½Π½ΡΡ
Π³Π΅Π½Π΅Π°Π»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π°, Π½Π΅Π²ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΎΡΠΌΠΎΡΡΠ°, ΠΌΠ°Π³Π½ΠΈΡΠ½ΠΎβΡΠ΅Π·ΠΎΠ½Π°Π½ΡΠ½ΠΎΠΉ ΡΠΎΠΌΠΎΠ³ΡΠ°ΡΠΈΠΈ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π° ΠΈ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ² ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎβΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π°.Π£ Π½Π°Π±Π»ΡΠ΄Π°Π΅ΠΌΠΎΠ³ΠΎ Π½Π°ΠΌΠΈ Π±ΠΎΠ»ΡΠ½ΠΎΠ³ΠΎ Π²ΡΡΠ²Π»Π΅Π½ΠΎ 2 Π²Π°ΡΠΈΠ°Π½ΡΠ° Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ Π² ΠΊΠΎΠΌΠΏΠ°ΡΠ½Π΄βΠ³Π΅ΡΠ΅ΡΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΠΎΠΌ ΡΠΎΡΡΠΎΡΠ½ΠΈΠΈ Π² Π³Π΅Π½Π΅ POLR3Π, ΠΊΠ°ΠΆΠ΄Π°Ρ ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ
Π±ΡΠ»Π° ΠΎΠΏΠΈΡΠ°Π½Π° ΡΠ°Π½Π΅Π΅ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π²Π°ΡΠΈΠ°Π±Π΅Π»ΡΠ½ΡΠΌΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΡΠΌΠΈ Π½Π΅ΠΉΡΠΎΠ΄Π΅Π³Π΅Π½Π΅ΡΠ°ΡΠΈΠ²Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. ΠΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΡΠΌΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ Ρ Π½Π°ΡΠ΅Π³ΠΎ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° Π±ΡΠ»ΠΈ ΠΌΠ°Π½ΠΈΡΠ΅ΡΡΠ°ΡΠΈΡ Π±ΠΎΠ»Π΅Π·Π½ΠΈ Π½Π° 1βΠΌ Π³ΠΎΠ΄Ρ ΠΆΠΈΠ·Π½ΠΈ, ΠΏΡΠ΅ΠΎΠ±Π»Π°Π΄Π°Π½ΠΈΠ΅ Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΠ°ΡΡΠΈΠ½Π΅ ΠΌΠΎΠ·ΠΆΠ΅ΡΠΊΠΎΠ²ΠΎΠΉ ΡΠΈΠΌΠΏΡΠΎΠΌΠ°ΡΠΈΠΊΠΈ, Π½Π°ΡΡΡΠ΅Π½ΠΈΠ΅ Π΄Π²ΠΈΠΆΠ΅Π½ΠΈΡ Π½ΠΈΠΆΠ½Π΅ΠΉ ΡΠ΅Π»ΡΡΡΠΈ, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠ΅Π΅ ΠΊ ΡΡΠΈΠ»Π΅Π½ΠΈΡ Π΄ΠΈΠ·Π°ΡΡΡΠΈΠΈ, Π·Π°Π΄Π΅ΡΠΆΠΊΠ° ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎΡΡΠΎΡΠ½Π½ΡΡ
Π·ΡΠ±ΠΎΠ² ΠΈ Π½ΠΈΠ·ΠΊΠΎΡΠΎΡΠ»ΠΎΡΡΡ. ΠΡΡΠ²Π»Π΅Π½Π½ΡΠ΅ ΠΏΡΠΈΠ·Π½Π°ΠΊΠΈ ΡΠΊΠ°Π·ΡΠ²Π°ΡΡ Π½Π° ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ Π±ΠΎΠ»Π΅Π·Π½ΠΈ ΡΡΠ΅Π΄Π½Π΅ΠΉ ΡΡΠΆΠ΅ΡΡΠΈ, ΡΡΠΎ ΡΠ²ΡΠ·Π°Π½ΠΎ Ρ ΡΠ°Π·Π½ΡΠΌ ΡΡΡΠ΅ΠΊΡΠΎΠΌ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Π½ΡΡ
Ρ ΠΏΡΠΎΠ±Π°Π½Π΄Π° ΠΌΡΡΠ°ΡΠΈΠΉ.POLR3ΠβΠ°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΡΡ ΡΠΎΠ±ΠΎΠΉ Π³ΡΡΠΏΠΏΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΡΡ
ΡΠΎΡΡΠΎΡΠ½ΠΈΠΉ, Π΄Π΅Π±ΡΡΠΈΡΡΡΡΠΈΡ
Ρ ΡΠ°Π½Π½Π΅Π³ΠΎ Π΄Π΅ΡΡΠΊΠΎΠ³ΠΎ Π΄ΠΎ Π²Π·ΡΠΎΡΠ»ΠΎΠ³ΠΎ Π²ΠΎΠ·ΡΠ°ΡΡΠ°. ΠΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΡ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ ΡΠΈΠΏΠ°ΠΌΠΈ ΠΈ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ ΠΌΡΡΠ°ΡΠΈΠΉ ΠΌΠΎΠ³ΡΡ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΎΠ²Π°ΡΡΡΡ ΠΈΠ·ΠΎΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΠΏΠ°ΡΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΡΠ°ΠΊΡΠΈΠ΅ΠΉ ΠΈΠ»ΠΈ ΡΠΎΡΠ΅ΡΠ°ΡΡΠ΅ΠΉΡΡ Ρ ΠΎΠ»ΠΈΠ³ΠΎΠ΄ΠΎΠ½ΡΠΈΠ΅ΠΉ ΠΈ Π³ΠΈΠΏΠΎΠ³ΠΎΠ½Π°Π΄ΠΎΡΡΠΎΠΏΠ½ΡΠΌ Π³ΠΈΠΏΠΎΠ³ΠΎΠ½Π°Π΄ΠΈΠ·ΠΌΠΎΠΌ, ΠΈΠ·ΠΎΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΠΈΠ»ΠΈ ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½Π½ΠΎΠΉ ΡΠΏΠ°ΡΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΠ°ΡΠ°ΠΏΠ»Π΅Π³ΠΈΠ΅ΠΉ, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΠΎΡΠ΅ΡΠ°Π½ΠΈΠ΅ΠΌ Π°ΡΠ°ΠΊΡΠΈΠΈ Ρ ΡΠΊΡΡΡΠ°ΠΏΠΈΡΠ°ΠΌΠΈΠ΄Π½ΡΠΌΠΈ ΡΠΈΠΌΠΏΡΠΎΠΌΠ°ΠΌΠΈ. ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π½ΠΎΠ΅ Π½Π°ΠΌΠΈ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΠ΅ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΡΠ΅Ρ ΡΠ»ΠΎΠΆΠ½ΠΎΡΡΡ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π±ΠΎΠ»Π΅Π·Π½ΠΈ Π² Π΄Π΅ΡΡΠΊΠΎΠΌ Π²ΠΎΠ·ΡΠ°ΡΡΠ΅, Π² ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π½Π°Π±ΠΎΡΠ° ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠΈΠΌΠΏΡΠΎΠΌΠΎΠ² ΠΈ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ½ΡΡ
ΠΏΡΠΈΠ·Π½Π°ΠΊΠΎΠ² ΠΏΡΠΈ Π²ΠΈΠ·ΡΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΌΠΎΠ·Π³Π°
- β¦