Observational Cohort Study of Dysferlinopathy in China

Peking University

Status: Completed

Conditions: Dysferlinopathy

Study type: Observational

Funder types: Other

Identifiers

NCT07035145

NSFC82301584

Details and patient eligibility

About

The cohort data to be collected aims to evaluate the phenotype, disease progression, natural history, as well as molecular, genetic, and morphological characteristics of dysferlinopathies (LGMD2B/Miyoshi) in China, contributing to the development of clinical outcome measures and the identification of potential biomarkers for future clinical trials.

Full description

Dysferlinopathy is an autosomal recessive myopathy caused by mutations in the DYSF gene. Dysferlinopathy represents a rare group of muscular dystrophies, characterized by the "core" phenotypes of Miyoshi Myopathy (MM), Limb-Girdle Muscular Dystrophy Type R2 (LGMDR2) and the rarer distal myopathy with anterior tibial involvement. As the disease progresses, involvement of both proximal and distal muscles is observed in many patients, deviating from the classic muscle weakness patterns of LGMD2B or Miyoshi Myopathy. In addition, the age at onset and the progression of muscle weakness exhibit considerable heterogeneity among patients. Compared to other types of muscular dystrophy, dysferlinopathy exhibits variable onset ages for wheelchair dependency and likely carries a lower risk of cardiac and respiratory complications. Therefore, detailed and regular assessments of motor function, along with follow-up, are essential for systematically understanding the disease progression and natural history of dysferlinopathy, as well as for providing data to support future clinical trials.

Dysferlinopathy is characterized by typical dystrophic pathological changes, including necrosis and regeneration of muscle fibers, hypertrophy and atrophy, as well as proliferation of connective tissue. The absence of DYSF protein expression on the sarcolemma is a key pathological hallmark and diagnostic criterion of dysferlinopathy. Moreover, inflammatory infiltration represents a significant pathological feature of this condition. Specific analysis of the immune environment in skeletal muscles may serve as a potential therapeutic target for dysferlinopathy in future research.

The Chinese dysferlinopathy patient registry is a nationwide, population-based observational cohort study encompassing dysferlinopathy patients across all age groups, collecting retrospective data at study entry and prospective data during follow-up. This registry is intended to contribute to the development of clinical outcome measures and the identification of potential biomarkers for future clinical trials.

Enrollment: 160 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female patients of all ages at baseline.
• Confirmed diagnosis of dysferlinopathy proven by i) two (predicted) pathogenic variations in DYSF gene, ii) one (predicted) pathogenic variation plus either absent dysferlin protein expression on muscle immunoblot. Mutations will be checked for pathogenicity via the UMD bioinformatics tools and and by checking the literature and mutation /variant databases.
• Ambulant with or without aids; or full-time wheelchair user, i.e. non-ambulant; with the ratio 2:1 between recruited ambulant and recruited non-ambulant patients.
• Ability to perform assessments (there will be different assessments for ambulant and non-ambulant patients).
• Informed consent to participate in the study.

Exclusion criteria

• Decline to participate.
• Other neuromuscular disease (such as Duchenne/Becker muscular dystrophy or Myotonic dystrophy).
• Serious systemic illness (such as cute cardiac, renal, hepatic insufficiency, myocardial infarction or an acute cerebrovascular accident (stroke) as well as infectious diseases).

Trial design

160 participants in 1 patient group

Dysferlinopathy

Description:

All patients with dysferlinopathy in China, irrespective of age. These dysferlinopathy patients were diagnosed according to i) two (predicted) pathogenic variations in DYSF gene, ii) one (predicted) pathogenic variation plus either absent dysferlin protein expression on muscle immunoblot (muscle biopsy was performed at Peking University First Hospital).