Evaluation of Clinical, Immunological, Morphological, Molecular and Genetic Characteristics of Patients With Limb-girdle Muscular Dystrophy Type R2 (Type 2B) in the Russian Federation

Сlinical status of patients with dysferlinopathy (MMT score)

时间窗: Through study completion at 24 months

Muscle strength will be assessed using MMT and will be expressed in points for each of the muscle groups assessed.

Сlinical status of patients with dysferlinopathy (6-minute walk test)

时间窗: Through study completion at 24 months

The participant will be asked to complete maximal distance in 6 minet as quickly as safely possible and the time in seconds is recorded.

Сlinical status of patients with dysferlinopathy (Hand Held Dynamometry).

时间窗: Through study completion at 24 months

Hand held dynamometry using the MicroFET2 myometer will be utilized to capture isometric muscle strength. Maximum strength in kilograms will be reported for each muscle group.

Clinical blood test. Level of RBC

时间窗: Through study completion at 24 months.

Level of RBC is planned to be assessed in patients with dysferlinopathy.

Biochemical blood test.

时间窗: Through study completion at 24 months

Levels of potassium (mmol/l) is planned to be assessed in patients with dysferlinopathy.

Biochemical blood test. Level of creatinine

时间窗: Through study completion at 24 months.

Level of creatinine (μmol/l) is planned to be assessed in patients with dysferlinopathy.

Biochemical blood test. Level of ALT

时间窗: Through study completion at 24 months.

Level of ALT (U/l) is planned to be assessed in patients with dysferlinopathy.

Blood cytokine levels in subjects with dysferlinopathy and healthy volunteers.

时间窗: Through study completion at 24 months

* To assess average blood cytokine levels in subjects with dysferlinopathy in various regions of the Russian Federation; * To assess average blood cytokine levels in healthy subjects. Blood serum cytokine profiling will be performed with the use of the multiparameter fluorescent diagnostic system Luminex 200 and the Bio-Plex Pro Human 27-Plex Panel (Bio-Rad, Hercules, USA) in accordance with the manufacturer's instructions. The data obtained will be processed with the use of MasterPlex CT control and MasterPlex QT analysis software (Hitachi Software, San Bruno, USA). The following cytokine Levels will be assessed in the study:FGF2, Eotaxin,G-CSF, GM-CSF, IFN-γ, IL-1β, 1IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 p70, IL-13, IL-15, IL-17, IP-10, MCP-1/MCAF, MIP-1α, MIP-1β,PDGF-BB, RANTES, TNF-α, VEGF.

Subpopulation compositions of T-lymphocytes in subjects with dysferlinopathy.

时间窗: Through study completion at 24 months

• To characterize changes in subpopulation compositions of T-lymphocytes in %.

Subpopulation compositions of phagocytic activity of leukocytes (a phagocytic index) in subjects with dysferlinopathy.

时间窗: Through study completion at 24 months

• To characterize changes in phagocytic activity of leukocytes (a phagocytic index).

Clinical blood test. Level of hematocrit

时间窗: Through study completion at 24 months.

Level of hematocrit (%) is planned to be assessed in patients with dysferlinopathy.

Clinical blood test. Level of platelets

时间窗: Through study completion at 24 months.

Level of platelets is planned to be assessed in patients with dysferlinopathy.

Biochemical blood test. Level of sodium

时间窗: Through study completion at 24 months.

Level of sodium (mmol/l) is planned to be assessed in patients with dysferlinopathy.

Biochemical blood test. Level of glucose

时间窗: Through study completion at 24 months.

Level of glucose (mmol/l) is planned to be assessed in patients with dysferlinopathy.

Clinical blood test (level of hemoglobin)

时间窗: Through study completion at 24 months.

Level of hemoglobin is planned to be assessed in patients with dysferlinopathy.

Clinical blood test. Levels of ESR

时间窗: Through study completion at 24 months.

Levels of ESR (mm/h) is planned to be assessed in patients with dysferlinopathy.

Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy (NBT test)

时间窗: Through study completion at 24 months

• To characterize changes in phagocytic activity of leukocytes (NBT test in CU).

Cardiac function (assessed by Electrocardiography). Outcome 13

时间窗: Through study completion at 24 months.

To assess rhythm characteristic, P-wave, QRS, T-wave duration; PR, RR, QT intervals; PR, ST segments.

Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent). Volumetric evaluation of EF

时间窗: Through study completion at 24 months.

Volumetric evaluation of EF by manual tracing will be performed.

Сlinical status of patients with dysferlinopathy ( North Star Assessment for dysferlinopathy)

时间窗: Through study completion at 24 months

North Star Assessment for Dysferlinopathy (NSAD) is a functional scale that will be used to measure motor performance in individuals with dysferlinopathy (includes 29 items).

Biochemical blood test. Level of calcium

时间窗: Through study completion at 24 months.

Level of calcium (mmol/l) is planned to be assessed in patients with dysferlinopathy.

Biochemical blood test. Level of uric acid

时间窗: Through study completion at 24 months.

Level of uric acid (μmol/l) is planned to be assessed in patients with dysferlinopathy.

Biochemical blood test. Level of CRP

时间窗: Through study completion at 24 months.

Level of CRP (mg/l) is planned to be assessed in patients with dysferlinopathy.

Muscle MRI in patients with dysferlinopathy.

时间窗: Through study completion at 24 months.

* To characterize muscle involvement based on MRI results; * To evaluate the progression of muscle involvement based on repeated MRI once year;

Clinical blood test. Level of WBC

时间窗: Through study completion at 24 months.

Level of WBC is planned to be assessed in patients with dysferlinopathy.

Biochemical blood test. Level of urea

时间窗: Through study completion at 24 months.

Level of urea (mmol/l) is planned to be assessed in patients with dysferlinopathy.

Biochemical blood test. Level of AST

时间窗: Through study completion at 24 months.

Level of AST (U/l) is planned to be assessed in patients with dysferlinopathy.

Biochemical blood test. Level of total protein

时间窗: Through study completion at 24 months.

Level of total protein (g/l) is planned to be assessed in patients with dysferlinopathy.

Biochemical blood test. Level of CPK

时间窗: Through study completion at 24 months.

Level of CPK (U/l) is planned to be assessed in patients with dysferlinopathy.

Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy (lysosomal-cation test).

时间窗: Through study completion at 24 months

• To characterize changes in phagocytic activity of leukocytes (lysosomal-cation test in CU).

Cardiac function (assessed by Echocardiography). Myocardium mass

时间窗: Through study completion at 24 months.

The absolute and relative sizes of the myocardium mass index will be determined.

Cardiac function (assessed by Echocardiography). LA

时间窗: Through study completion at 24 months.

The absolute and relative sizes of the left atrium (LA) index will be determined

Biochemical blood test. Level of triglycerides

时间窗: Through study completion at 24 months.

Level of triglycerides (mmol/l) is planned to be assessed in patients with dysferlinopathy.

Autoantibodies in patients with dysferlinopathy.

时间窗: Through study completion at 24 months

Assessment of antibodу level against skeletal muscle antigens; an antinuclear factor (ANA), an extractable nuclear antigen.

Subpopulation compositions of B-lymphocytes in subjects with dysferlinopathy.

时间窗: Through study completion at 24 months

• To characterize changes in subpopulation compositions of B-lymphocytes in %.

Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy.

时间窗: Through study completion at 24 months

• To characterize changes in phagocytic activity of leukocytes (a phagocyte number in CU).

Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent).

时间窗: Through study completion at 24 months.

Volumetric evaluation of volume by manual tracing will be performed.

Gait pattern and balance characteristics in patients with limb-girdle muscular dystrophy R2.

时间窗: Through study completion at 24 months.

To determine a gait pattern characteristics in patients with limb-girdle muscular dystrophy R2 using electrophysiological techniques (Neurosoft Gait Assessment System "STEDIS").

Cardiac function (assessed by Echocardiography). LV

时间窗: Through study completion at 24 months.

The absolute and relative sizes of the left ventricle (LV) index will be determined.

Cardiac function (assessed by Echocardiography). LV mass

时间窗: Through study completion at 24 months.

The absolute and relative sizes of the LV mass index will be determined.

Cardiac function (assessed by Echocardiography). RV

时间窗: Through study completion at 24 months.

The absolute and relative sizes of the right ventricle (RV) index will be determined.

Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent). Volumetric evaluation of LV mass

时间窗: Through study completion at 24 months.

Volumetric evaluation of LV mass by manual tracing will be perform. An MRI of the heart will assess fibrosis.

Morphological muscle study

时间窗: Through study completion at 24 months.

If it was necessary to confirm the causation of mutations in the dysferlin gene, the patients underwent muscle biopsy. To study the expression (immunohistochemistry and western-blotting) and distribution of dysferlin in impaired muscles of subjects with LGMDR2.