62 research outputs found
Π‘ΠΈΠ½Π΄ΡΠΎΠΌ ΠΠ°ΠΌΠ±βΠ¨Π°ΡΡΠ΅ΡΠ°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΠΉ ΡΠ°Π½Π΅Π΅ Π½Π΅ ΠΎΠΏΠΈΡΠ°Π½Π½ΠΎΠΉ ΠΌΡΡΠ°ΡΠΈΠ΅ΠΉ Π² Π³Π΅Π½Π΅ SOX5
Clinical and genetic characteristics of a patient with LambβShaffer syndrome due to the newly discovered heterozygous missense mutation p.1868A>C in the 14 exon of the SOX5 gene are presented in the next generation sequencing of exom. It is shown that, in contrast to the previously described patients due to the presence of a deletion in the region of the gene or segment of chromosome 12p12.1, in the presence of missense mutation, the intellectual deficit and the dysmorphic features of the structure are not pronounced sharply and there is no anomaly in the development of other organs and systems.ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ Π±ΠΎΠ»ΡΠ½ΠΎΠ³ΠΎ Ρ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ ΠΠ°ΠΌΠ±βΠ¨Π°ΡΡΠ΅ΡΠ°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΠΌ Π²ΠΏΠ΅ΡΠ²ΡΠ΅ Π²ΡΡΠ²Π»Π΅Π½Π½ΠΎΠΉ Π³Π΅ΡΠ΅ΡΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΠΎΠΉ ΠΌΠΈΡΡΠ΅Π½Ρ-ΠΌΡΡΠ°ΡΠΈΠ΅ΠΉ Ρ.1868Π>Π‘ Π² ΡΠΊΠ·ΠΎΠ½Π΅ 14 Π³Π΅Π½Π° SOX5 ΠΏΡΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΊΠ·ΠΎΠΌΠ° Π½ΠΎΠ²ΠΎΠ³ΠΎ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΡ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π² ΠΎΡΠ»ΠΈΡΠΈΠ΅ ΠΎΡ ΡΠ°Π½Π΅Π΅ ΠΎΠΏΠΈΡΠ°Π½Π½ΡΡ
Π±ΠΎΠ»ΡΠ½ΡΡ
c ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ ΠΠ°ΠΌΠ±βΠ¨Π°ΡΡΠ΅ΡΠ°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΠΌ Π½Π°Π»ΠΈΡΠΈΠ΅ΠΌ Π΄Π΅Π»Π΅ΡΠΈΠΈ Π² ΠΎΠ±Π»Π°ΡΡΠΈ Π³Π΅Π½Π° ΠΈΠ»ΠΈ ΡΡΠ°ΡΡΠΊΠ° Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ 12Ρ12.1, ΠΏΡΠΈ ΠΌΠΈΡΡΠ΅Π½Ρ-ΠΌΡΡΠ°ΡΠΈΠΈ ΠΈΠ½ΡΠ΅Π»Π»Π΅ΠΊΡΡΠ°Π»ΡΠ½ΡΠΉ Π΄Π΅ΡΠΈΡΠΈΡ ΠΈ Π΄ΠΈΡΠΌΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ΅ΡΡΡ ΡΡΡΠΎΠ΅Π½ΠΈΡ Π²ΡΡΠ°ΠΆΠ΅Π½Ρ Π½Π΅ΡΠ΅Π·ΠΊΠΎ ΠΈ ΠΎΡΡΡΡΡΡΠ²ΡΡΡ Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ Π΄ΡΡΠ³ΠΈΡ
ΠΎΡΠ³Π°Π½ΠΎΠ² ΠΈ ΡΠΈΡΡΠ΅ΠΌ.
ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΠΈ Π°Π»Π³ΠΎΡΠΈΡΠΌ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΡΡΡΠΈΡ ΠΌΡΡΠ΅ΡΠ½ΡΡ Π΄ΠΈΡΡΡΠΎΡΠΈΠΉ, ΠΌΠ°Π½ΠΈΡΠ΅ΡΡΠΈΡΡΡΡΠΈΡ ΠΏΠΎΡΠ»Π΅ ΠΏΠ΅ΡΠΈΠΎΠ΄Π° Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΌΠΎΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ
Background. Progressive muscular dystrophies (PMD) are a group of genetically heterogeneous diseases that manifest in the age range from early childhood to adulthood. Depending on the predominant topography of the muscular lesion, there are: limb-girdle, distal, oculopharyngeal, facial-shoulder-scapular-peroneal variants of PMD.Aim. Creation of algorithms for the differential diagnosis of PMD with multiple topography of muscle lesions.Materials and methods. We observed 192 patients aged 1.5 to 66 years with PMD with a debut after a period of normal motor development. The diagnosis was established on the basis of genealogical analysis, neurological examination, assessment of non-muscular manifestations, results of instrumental, biochemical molecular genetic studies.Results. Four groups of patients were identified, differing in the topography of muscle damage and 19 genetic variants of PMD were diagnosed. An algorithm for diagnosing PMD that manifest after a period of normal motor development is proposed, which is based on the frequency of occurrence of individual genetic variants and their proportion in the analyzed sample, the presence of major mutations in causal genes, the features of phenotypic characteristics, the gender of the patient and the possibility of conducting etiopathogenetic therapy developed by for some genetic variants.Conclusion. The use of the proposed algorithm in clinical practice can significantly reduce the economic and time costs for confirmatory molecular genetic diagnosis, and promptly recommend etiopathogenetic therapy for some genetic variants of this group of diseases.Β ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΡΡΡΠΈΠ΅ ΠΌΡΡΠ΅ΡΠ½ΡΠ΅ Π΄ΠΈΡΡΡΠΎΡΠΈΠΈ (ΠΠΠ) β Π³ΡΡΠΏΠΏΠ° Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈ Π³Π΅ΡΠ΅ΡΠΎΠ³Π΅Π½Π½ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, ΠΌΠ°Π½ΠΈΡΠ΅ΡΡΠΈΡΡΡΡΠΈΡ
Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ½ΠΎΠΌ Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ ΠΎΡ ΡΠ°Π½Π½Π΅Π³ΠΎ Π΄Π΅ΡΡΠΊΠΎΠ³ΠΎ Π΄ΠΎ Π²Π·ΡΠΎΡΠ»ΠΎΠ³ΠΎ Π²ΠΎΠ·ΡΠ°ΡΡΠ°. Π Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΡΠΎΠΏΠΎΠ³ΡΠ°ΡΠΈΠΈ ΠΌΡΡΠ΅ΡΠ½ΠΎΠ³ΠΎ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΡ Π²ΡΠ΄Π΅Π»ΡΡΡ ΠΏΠΎΡΡΠ½ΠΎ-ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠ½ΡΠ΅, Π΄ΠΈΡΡΠ°Π»ΡΠ½ΡΠ΅, ΠΎΠΊΡΠ»ΠΎΡΠ°ΡΠΈΠ½Π³Π΅Π°Π»ΡΠ½ΡΠ΅, Π»ΠΈΡΠ΅-ΠΏΠ»Π΅ΡΠ΅-Π»ΠΎΠΏΠ°ΡΠΎΡΠ½ΠΎ-ΠΏΠ΅ΡΠΎΠ½Π΅Π°Π»ΡΠ½ΡΠ΅ Π²Π°ΡΠΈΠ°Π½ΡΡ ΠΠΠ.Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β ΡΠΎΠ·Π΄Π°Π½ΠΈΠ΅ Π°Π»Π³ΠΎΡΠΈΡΠΌΠΎΠ² Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΠΠ Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΠΎΠΉ ΡΠΎΠΏΠΎΠ³ΡΠ°ΡΠΈΠ΅ΠΉ ΠΌΡΡΠ΅ΡΠ½ΠΎΠ³ΠΎ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΡ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠΎΠ΄ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΠ΅ΠΌ Π½Π°Ρ
ΠΎΠ΄ΠΈΠ»ΠΈΡΡ 192 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ ΠΎΡ 1,5 Π΄ΠΎ 66 Π»Π΅Ρ Ρ ΠΠΠ Ρ Π΄Π΅Π±ΡΡΠΎΠΌ ΠΏΠΎΡΠ»Π΅ ΠΏΠ΅ΡΠΈΠΎΠ΄Π° Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΌΠΎΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ. ΠΠΈΠ°Π³Π½ΠΎΠ· ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ² Π³Π΅Π½Π΅Π°Π»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π°, Π½Π΅Π²ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΎΡΠΌΠΎΡΡΠ°, ΠΎΡΠ΅Π½ΠΊΠΈ Π²Π½Π΅ΠΌΡΡΠ΅ΡΠ½ΡΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ, ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΡ
, Π±ΠΈΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΠ΄Π΅Π»Π΅Π½ΠΎ 4 Π³ΡΡΠΏΠΏΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΡΠ°Π·Π»ΠΈΡΠ°ΡΡΠΈΡ
ΡΡ ΠΏΠΎ ΡΠΎΠΏΠΎΠ³ΡΠ°ΡΠΈΠΈ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΡ ΠΌΡΡΡ, ΠΈ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠΎΠ²Π°Π½ΠΎ 19 Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² ΠΠΠ. ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½ Π°Π»Π³ΠΎΡΠΈΡΠΌ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΠΠ, ΠΌΠ°Π½ΠΈΡΠ΅ΡΡΠΈΡΡΡΡΠΈΡ
ΠΏΠΎΡΠ»Π΅ ΠΏΠ΅ΡΠΈΠΎΠ΄Π° Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΌΠΎΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ, Π² ΠΎΡΠ½ΠΎΠ²Ρ ΠΊΠΎΡΠΎΡΠΎΠ³ΠΎ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½Ρ ΡΠ°ΡΡΠΎΡΡ Π²ΡΡΡΠ΅ΡΠ°Π΅ΠΌΠΎΡΡΠΈ ΠΎΡΠ΄Π΅Π»ΡΠ½ΡΡ
Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² ΠΈ ΠΈΡ
Π΄ΠΎΠ»Π΅Π²Π°Ρ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π½ΠΎΡΡΡ Π² Π°Π½Π°Π»ΠΈΠ·ΠΈΡΡΠ΅ΠΌΠΎΠΉ Π²ΡΠ±ΠΎΡΠΊΠ΅, Π½Π°Π»ΠΈΡΠΈΠ΅ ΠΌΠ°ΠΆΠΎΡΠ½ΡΡ
ΠΌΡΡΠ°ΡΠΈΠΉ Π² ΠΊΠ°ΡΠ·Π°Π»ΡΠ½ΡΡ
Π³Π΅Π½Π°Ρ
, ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΡΠ΅Π½ΠΎΡΠΈΠΏΠΈΡΠ΅ΡΠΊΠΈΡ
Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊ, ΠΏΠΎΠ» Π±ΠΎΠ»ΡΠ½ΠΎΠ³ΠΎ ΠΈ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΡΡΠΈΠΎΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ, ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΠΎΠΉ Π΄Π»Ρ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ².ΠΡΠ²ΠΎΠ΄Ρ. ΠΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π½ΠΎΠ³ΠΎ Π°Π»Π³ΠΎΡΠΈΡΠΌΠ° Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠ΅ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΡΠ½ΠΈΠ·ΠΈΡΡ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ Π²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ Π·Π°ΡΡΠ°ΡΡ Π½Π° ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π°ΡΡΠ΅ΠΉ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈ ΡΠ²ΠΎΠ΅Π²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄ΠΎΠ²Π°ΡΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ ΡΡΠΈΠΎΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΏΡΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π²Π°ΡΠΈΠ°Π½ΡΠ°Ρ
ΡΡΠΎΠΉ Π³ΡΡΠΏΠΏΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ.
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
ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΠΠΎΡβΠΡΠ½ΡΡΡΠ°βΠ¨Π°Π°ΡΠ°, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΠΎΠ³ΠΎ Π²Π½ΠΎΠ²Ρ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΠΌΠΈ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ NR2F1
BoschβBoonstraβSchaaf optic atrophy is autosomal dominant disorder caused by mutations in the NR2F1 gene. Its common features include optic atrophy and / or hypoplasia, developmental delay, intellectual disability, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, hypotonia, and thinning of the corpus callosum. We report of the clinical and genetic characteristics of two patients with Bosch-Boonstra-Schaaf syndrome with newly detected of the missense mutations Ρ.329T>C (p.Phe110Ser) and Ρ.413G>A (p.Cys138Tyr) in the gene NR2F1. The existence of a polymorphism of the clinical manifestations of the syndrome has been shown, and the necessity of using exome sequencing in the diagnosis of neuro-ophthalmic diseases has been substantiated.Π‘ΠΈΠ½Π΄ΡΠΎΠΌ ΠΠΎΡβΠΡΠ½ΡΡΡΠ°βΠ¨Π°Π°ΡΠ° β Π°ΡΡΠΎΡΠΎΠΌΠ½ΠΎ-Π΄ΠΎΠΌΠΈΠ½Π°Π½ΡΠ½ΠΎΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΠΎΠ΅ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π³Π΅Π½Π΅ NR2F1. ΠΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΡ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΡΡΡΡ ΡΠΎΡΠ΅ΡΠ°Π½ΠΈΠ΅ΠΌ Π°ΡΡΠΎΡΠΈΠΈ ΠΈ / ΠΈΠ»ΠΈ Π³ΠΈΠΏΠΎΠΏΠ»Π°Π·ΠΈΠΈ Π·ΡΠΈΡΠ΅Π»ΡΠ½ΡΡ
Π½Π΅ΡΠ²ΠΎΠ², Π·Π°Π΄Π΅ΡΠΆΠΊΠΎΠΉ ΠΌΠΎΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ, ΠΈΠ½ΡΠ΅Π»Π»Π΅ΠΊΡΡΠ°Π»ΡΠ½ΡΠΌ Π΄Π΅ΡΠΈΡΠΈΡΠΎΠΌ, ΡΡΠ΄ΠΎΡΠΎΠ³Π°ΠΌΠΈ, Π³ΠΈΠΏΠΎΡΠΎΠ½ΠΈΠ΅ΠΉ ΠΈ Π³ΠΈΠΏΠΎΠΏΠ»Π°Π·ΠΈΠ΅ΠΉ ΠΌΠΎΠ·ΠΎΠ»ΠΈΡΡΠΎΠ³ΠΎ ΡΠ΅Π»Π°. Π ΡΡΠ°ΡΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΎ ΠΎΠΏΠΈΡΠ°Π½ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊ 2 Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ ΠΠΎΡβΠΡΠ½ΡΡΡΠ°βΠ¨Π°Π°ΡΠ° Ρ Π²Π½ΠΎΠ²Ρ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΠΌΠΈ ΠΌΠΈΡΡΠ΅Π½Ρ-ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Ρ.329Π’>Π‘ (p.Phe110Ser) ΠΈ Ρ.413G>A (p.Cys138Tyr) Π² Π³Π΅Π½Π΅ NR2F1. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ ΡΡΡΠ΅ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠ° ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΠΈ ΠΎΠ±ΠΎΡΠ½ΠΎΠ²Π°Π½Π° Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΊΠ·ΠΎΠΌΠ° Π² Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ΅ Π½Π΅ΠΉΡΠΎΠΎΡΡΠ°Π»ΡΠΌΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ
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
ΠΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΡΡ Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² ΠΌΠ»Π°Π΄Π΅Π½ΡΠ΅ΡΠΊΠΎΠΉ ΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΠΈ
One of the most common neurological symptoms in children of the first year of life is seizures, the etiology of which is manifold. Investigations in recent years have shown that a significant number of infantile seizures are hereditary in nature. The review identifies the main groups of hereditary diseases and syndromes, in whose symptom complex convulsions are observed, outlines the main features of their clinical manifestations and methods of diagnosis. Correct and timely diagnosis of hereditary pathology helps not only to determine the nature of the course of the disease and the effectiveness of the use of various antiepileptic drugs, but also to significantly improve the effectiveness of genetic counseling of burdened families and to prevent the occurrence of recurrent cases ΠΎf disease.Β Π‘ΡΠ΄ΠΎΡΠΎΠ³ΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΠΎΠΉ ΡΡΠΈΠΎΠ»ΠΎΠ³ΠΈΠΈ ΡΠ²Π»ΡΡΡΡΡ ΠΎΠ΄Π½ΠΈΠΌ ΠΈΠ· ΡΠ°ΠΌΡΡ
ΡΠ°ΡΡΡΡ
Π½Π΅Π²ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠΈΠΌΠΏΡΠΎΠΌΠΎΠ² Ρ Π΄Π΅ΡΠ΅ΠΉ ΠΏΠ΅ΡΠ²ΠΎΠ³ΠΎ Π³ΠΎΠ΄Π° ΠΆΠΈΠ·Π½ΠΈ. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΡ
Π»Π΅Ρ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ Π² Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π΅ ΡΠ»ΡΡΠ°Π΅Π² ΡΡΠ΄ΠΎΡΠΎΠ³ΠΈ Ρ ΠΌΠ»Π°Π΄Π΅Π½ΡΠ΅Π² ΠΈΠΌΠ΅ΡΡ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΡΡ ΠΏΡΠΈΡΠΎΠ΄Ρ. Π Π΄Π°Π½Π½ΠΎΠΌ ΠΎΠ±Π·ΠΎΡΠ΅ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ Π³ΡΡΠΏΠΏΡ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΡΡ
Π±ΠΎΠ»Π΅Π·Π½Π΅ΠΉ ΠΈ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠ², Π² ΡΠΈΠΌΠΏΡΠΎΠΌΠΎΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ΅ ΠΊΠΎΡΠΎΡΡΡ
Π½Π°Π±Π»ΡΠ΄Π°ΡΡΡΡ ΡΡΠ΄ΠΎΡΠΎΠ³ΠΈ, ΠΈΠ·Π»ΠΎΠΆΠ΅Π½Ρ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΠΈΡ
ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ ΠΈ ΡΠΏΠΎΡΠΎΠ±Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ. ΠΡΠ°Π²ΠΈΠ»ΡΠ½Π°Ρ ΠΈ ΡΠ²ΠΎΠ΅Π²ΡΠ΅ΠΌΠ΅Π½Π½Π°Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ° Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΈ ΠΏΠΎΠΌΠΎΠ³Π°Π΅Ρ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡ Ρ
Π°ΡΠ°ΠΊΡΠ΅Ρ ΡΠ΅ΡΠ΅Π½ΠΈΡ Π±ΠΎΠ»Π΅Π·Π½ΠΈ ΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ ΡΠ°Π·Π½ΡΡ
ΠΏΡΠΎΡΠΈΠ²ΠΎΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ², Π° ΡΠ°ΠΊΠΆΠ΅ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΠΏΠΎΠ²ΡΡΠΈΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΌΠ΅Π΄ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΊΠΎΠ½ΡΡΠ»ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΎΡΡΠ³ΠΎΡΠ΅Π½Π½ΡΡ
ΡΠ΅ΠΌΠ΅ΠΉ ΠΈ ΠΎΡΡΡΠ΅ΡΡΠ²ΠΈΡΡ ΠΏΡΠΎΡΠΈΠ»Π°ΠΊΡΠΈΠΊΡ Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΡ ΠΏΠΎΠ²ΡΠΎΡΠ½ΡΡ
ΡΠ»ΡΡΠ°Π΅Π² Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ.
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
Π‘ΠΈΠ½Π΄ΡΠΎΠΌ ΡΠΈΠ³ΠΈΠ΄Π½ΠΎΠ³ΠΎ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° Ρ Π΄Π΅Π±ΡΡΠΎΠΌ Π² Π³ΡΡΠ΄Π½ΠΎΠΌ Π²ΠΎΠ·ΡΠ°ΡΡΠ΅
The case of stiff-person syndrome with benign course in 16-years old patient is presented. The initial clinical signs of the disease were observed in infancy with retarded development of motor functions and skeleton muscle lumps. The diagnosis was made using generally accepted clinical and electromyographical criteria. Aspects of differential diagnosis, pathogenesis and clinical course polymorphism in early-onset cases of the disease are discussed.ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ ΡΠ»ΡΡΠ°ΠΉ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΡΠΈΠ³ΠΈΠ΄Π½ΠΎΠ³ΠΎ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° Ρ Π΄ΠΎΠ±ΡΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠΌ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ΠΌ Ρ ΠΏΠΎΠ΄ΡΠΎΡΡΠΊΠ° 16 Π»Π΅Ρ. ΠΠ΅Π±ΡΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΠΎΡΠΌΠ΅ΡΠ΅Π½ Π² Π³ΡΡΠ΄Π½ΠΎΠΌ Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ Π² Π²ΠΈΠ΄Π΅ Π·Π°Π΄Π΅ΡΠΆΠΊΠΈ ΡΠ΅ΠΌΠΏΠΎΠ² ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΌΠΎΡΠΎΡΠ½ΡΡ
ΡΡΠ½ΠΊΡΠΈΠΉ ΠΈ ΡΠΏΠ»ΠΎΡΠ½Π΅Π½ΠΈΠΉ ΡΠΊΠ΅Π»Π΅ΡΠ½ΡΡ
ΠΌΡΡΡ. ΠΠΈΠ°Π³Π½ΠΎΠ· ΡΡΠΎΡΠΌΡΠ»ΠΈΡΠΎΠ²Π°Π½ Π² ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΈΠΈ Ρ ΠΎΠ±ΡΠ΅ΠΏΡΠΈΠ½ΡΡΡΠΌΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΈ ΡΠ»Π΅ΠΊΡΡΠΎΠΌΠΈΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΊΡΠΈΡΠ΅ΡΠΈΡΠΌΠΈ. ΠΠ±ΡΡΠΆΠ΄Π΅Π½Ρ Π²ΠΎΠΏΡΠΎΡΡ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ Π΄ΠΈΠ°Π³Π½ΠΎΠ·Π° ΠΈ ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π°, ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠ° ΡΠ΅ΡΠ΅Π½ΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ Π² ΡΠ»ΡΡΠ°ΡΡ
ΡΠ°Π½Π½Π΅ΠΉ ΠΌΠ°Π½ΠΈΡΠ΅ΡΡΠ°ΡΠΈΠΈ ΡΠΈΠΌΠΏΡΠΎΠΌΠΎΠ²
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