Clinical, Immunological, Morphological and Genetic Characteristics of Patients With Dysferlinopathy (LGMD R2) in the RF

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

To evaluate specific characteristics of phenotype, immune status, molecular and genetic as well as morphological characteristics of adult patients with limb-girdle muscular dystrophy R2 in various regions of the Russian Federation.

A single-center, cohort clinical study. Subjects of both sexes aged 18 to 65 inclusive with genetically confirmed diagnosis of limb-girdle muscular dystrophy type R2, who have signed the written informed consent form for this study.

The control and case groups should be age- and gender-matched.

Study Objectives:

• To evaluate a clinical status of a subject (MMT score; 6-minute walk test; North Star Assessment for dysferlinopathy (NSAD));
• To assess blood biochemistry;
• To characterize muscle involvement based on MRI results;
• To evaluate the progression of muscle involvement based on repeated MRI;
• To assess cardiac function with ECG, EchoCG and MRI;
• To determine a gait pattern and balance characteristics in patients with limb-girdle muscular dystrophy using electrophysiological techniques (Neurosoft Gait Assessment System Steadys; stabilometrics and plantography with "SIDAS");
• To characterize changes in subpopulation compositions of T- and B-lymphocytes, phagocytic activity of leukocytes (a phagocytic index, a phagocyte number, an index of phagocytosis completeness, lysosomal-cation and NBT tests);
• To assess average blood cytokine levels in subjects with limb-girdle muscular dystrophy (type R2) in various regions of the Russian Federation;
• To assess average blood cytokine levels in healthy subjects from various regions of the RF;
• To analyze the relationship between blood cytokine levels and the presence of a mutation in the dysferlin gene;
• To study the expression (immunohistochemistry and western-blotting) and distribution of dysferlin in impaired muscles of subjects with LGMDR2.

The clinical study includes the stages as follows:

1. Subject enrollment - 24 months
2. Data collection and analysis - 12 months
3. Study Report - 30 days.

Inclusion Criteria:

• 18 to 85 (inclusive) years-old subjects of both sexes;
• A signed written informed consent form;
• Genetically confirmed diagnosis of limb-girdle muscular dystrophy (type 2B) (a case group)

Exclusion Criteria:

• A subject who is an investigator, study assistant, study coordinator and a member of the other personnel indirectly or directly associated with the conduct of the study;
• Acute medical conditions associated with visceral dysfunction, life-threatening conditions which occurred less than 6 months prior to enrollment into the study such as acute cardiac, renal, hepatic insufficiency, myocardial infarction or an acute cerebrovascular accident (stroke) as well as infectious diseases;
• Excessive alcohol consumption (> 20 g/day).