The objective of the study is to answer the following important questions. Deficiency of the dysferlin protein is the cause of a very rare limb-girdle muscular dystrophy (LGMD-2B) that leads to significant disability. This disease is caused by mutations in the dysferlin gene. It is a recessive inherited disease, meaning that both copies of the gene must have mutations for the disease to develop. This study aims to analyze the frequency of carriers of a mutation in the DYSF gene in the Caucasian population. To achieve this, The investigator analyzed the blood of 100 healthy volunteers from their local area, quantifying the dysferlin protein in peripheral blood monocytes.

Inclusion Criteria:

• Individuals diagnosed with dysferlinopathies.
• Carriers of a single mutation in the DYSF gene.
• Participants who are willing to undergo treatment with oral vitamin D3.
• Subjects who can provide informed consent for participation in the study.
• Controls and carriers willing to participate in in vitro studies using HL60 cells, monocytes, and myotubes.

Exclusion Criteria:

• Individuals with conditions or medications that could interfere with the study outcomes of dysferlin expression.
• Participants who are unwilling or unable to adhere to the study protocol for the duration of the study period.
• Pregnant or breastfeeding women.
• Individuals with known allergies or adverse reactions to vitamin D3 supplements.
• Subjects with severe concurrent illnesses that may impact the study's objectives or their ability to participate effectively.

The study focuses on individuals with dysferlinopathies, a heterogeneous group of autosomal recessive muscular dystrophies caused by mutations in the DYSF gene. It examines the effect of vitamin D3 treatment on dysferlin expression in vitro using HL60 cells, monocytes, and myotubes from controls and carriers of a single DYSF mutation. Additionally, an observational study with oral vitamin D3 in a cohort of 21 carriers demonstrates a significant increase in dysferlin expression in treated monocytes compared to untreated carriers. These findings suggest significant therapeutic implications, emphasizing the potential of combining molecular strategies with vitamin D3 supplementation to elevate dysferlin expression to non-pathological levels.