Symptomatic dysferlin gene mutation carriers: characterization of two cases

Area of Science:

• Neurology
• Genetics
• Biochemistry

Background:

• Dysferlin gene mutations cause muscular dystrophies like limb girdle muscular dystrophy 2B and Miyoshi myopathy.
• Carrier status for these mutations is typically asymptomatic, but symptomatic cases can occur.

Observation:

• Two patients with symptomatic muscle weakness were identified as dysferlin mutation carriers.
• One patient had limb girdle weakness, and the other had distal weakness.
• Genetic analysis revealed mutations in the dysferlin gene in both patients.

Findings:

• Both patients exhibited elevated creatine kinase and abnormal muscle MRI findings.
• Muscle biopsies showed dystrophic changes and reduced sarcolemmal dysferlin expression.
• Western blot analysis confirmed significantly reduced dysferlin protein levels in both skeletal muscle and peripheral blood monocytes (PBMs).
• Dysferlin mRNA levels were normal, indicating a post-transcriptional defect.

Implications:

• The study highlights the importance of considering symptomatic carriers in the differential diagnosis of muscular weakness.
• Detecting reduced dysferlin protein in PBMs may serve as a diagnostic biomarker for symptomatic carriers.
• Understanding dysferlinopathy in carriers can inform genetic counseling and patient management.