Distal Myopathy With Anterior Tibial Onset, Limb-Girdle Muscular Dystrophy Type 2B, Miyoshi Myopathy, Muscular Dystrophies
Conditions
Keywords
muscular dystrophy, dysferlin, Limb-Girdle Muscular Dystrophy Type 2B, Miyoshi Myopathy, Distal Myopathy with Anterior Tibial Onset
Brief summary
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.
Interventions
DIAGNOSTIC_TESTProtein analysis
The investigator enrolled 149 healthy volunteers and collected peripheral blood samples for protein analysis. While 18 of these individuals with protein levels in the range of 40%-64% were predicted to be carriers by the monocyte assay, subsequent DYSF sequencing analysis in 14 of 18 detected missense variants in only four. Analysis of DNA methylation patterns at the DYSF locus showed no changes in methylation levels at CpG islands and shores between samples.
Sponsors
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dysferlin Expression Levels by age and gender | 1 month | Dysferlin expresion lels in monocytes by western blotting |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Identification of Carries by Protein Level | 1 month | Identification of Carries by Protein Level |
| Percentage of Predicted Carriers Showing Specific Genetic Mutations | 1 month | Mutation Analysis of Predicted Carriers |
| Percentage of DNA Methylation in Target Gene | 1 month | DNA Methylation status of the DYSF locus in order to determine wether the reduced DYSF levels in carrier and disease range had an underlying epigenetic mechanism. |
Countries
Spain
Outcome results
None listed