Dysferlinopathy Protein in Peripheral Blood Monocytes.

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau149 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

149

Conditions

Muscular Dystrophies Limb-Girdle Muscular Dystrophy Type 2B Miyoshi Myopathy Distal Myopathy With Anterior Tibial Onset

Interventions

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.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Dysferlin Expression Levels by age and gender

Dysferlin expresion lels in monocytes by western blotting

Time frame: 1 month

Secondary Outcomes

Identification of Carries by Protein Level

Time frame: 1 month

Percentage of Predicted Carriers Showing Specific Genetic Mutations

Mutation Analysis of Predicted Carriers

Time frame: 1 month

Percentage of DNA Methylation in Target Gene

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.

Time frame: 1 month

Dysferlinopathy Protein in Peripheral Blood Monocytes.

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes