Dysferlinopathy Protein in Peripheral Blood Monocytes.

Cross-sectional Study to Evaluate the Frequency of Dysferlinopathy Carriers in the Caucasian Population Using a Test for Detecting the Dysferlin Protein in Peripheral Blood Monocytes.

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 Overview

• Status: Completed
• Conditions: Muscular Dystrophies; Miyoshi Myopathy; Limb-Girdle Muscular Dystrophy Type 2B; Distal Myopathy With Anterior Tibial Onset
• Intervention / Treatment: Diagnostic test: Protein analysis

• Study Type: Observational
• Enrollment (Actual): 149

Contacts and Locations

Study Locations

• Spain
  • Cataluña
    • Barcelona, Cataluña, Spain, 08041
      • Eduard Gallardo Vigo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dysferlin Expression Levels by age and gender	Dysferlin expresion lels in monocytes by western blotting	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of Carries by Protein Level	Identification of Carries by Protein Level	1 month
Percentage of Predicted Carriers Showing Specific Genetic Mutations	Mutation Analysis of Predicted Carriers	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.	1 month

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2012
• Primary Completion (Actual): February 27, 2012
• Study Completion (Actual): July 17, 2017

Study Registration Dates

• First Submitted: July 5, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): July 18, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: muscular dystrophy; Miyoshi Myopathy; dysferlin; Limb-Girdle Muscular Dystrophy Type 2B; Distal Myopathy with Anterior Tibial Onset
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Diseases; Muscular Dystrophies, Limb-Girdle; Distal Myopathies
• Other Study ID Numbers: IIBSP-MON-2011-157

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No