Dysferlinopathy Protein in Peripheral Blood Monocytes.

NCT06507215 | Completed

• 1 other identifier: IIBSP-MON-2011-157
• Study Type: observational
• Target: 149
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

muscular dystrophy; dysferlin; Limb-Girdle Muscular Dystrophy Type 2B; Miyoshi Myopathy; Distal Myopathy with Anterior Tibial Onset

Outcome Measures

Primary Outcomes (1)

• Dysferlin Expression Levels by age and gender

  Dysferlin expresion lels in monocytes by western blotting

  1 month

Secondary Outcomes (3)

• Identification of Carries by Protein Level

  1 month

• Percentage of Predicted Carriers Showing Specific Genetic Mutations

  1 month

• Percentage of DNA Methylation in Target Gene

  1 month

Interventions

Protein analysis DIAGNOSTIC_TEST

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 Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Eduard Gallardo Vigo

Barcelona, Catalonia, 08041, Spain

Location

MeSH Terms

Conditions

Muscular Dystrophies; Limb-girdle muscular dystrophy, type 2B; Miyoshi myopathy; Myopathy, Distal, with Anterior Tibial Onset

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2024
• First Posted: July 18, 2024
• Study Start: February 1, 2012
• Primary Completion: February 27, 2012
• Study Completion: July 17, 2017
• Last Updated: July 18, 2024

Record last verified: 2024-07

Locations

ES (1)