Clinical Phenotype Spectrum in Two Large Chinese Families With Rippling Muscle Disease Caused by CAV-3 c.80G>A

Area of Science:

• Neurology
• Genetics
• Muscle Diseases

Background:

• Rippling muscle disease (RMD) is a rare myotonic myopathy.
• It is caused by pathogenic variants in the caveolin-3 (CAV-3) gene.
• A comprehensive understanding of RMD's phenotypic spectrum is lacking.

Purpose of the Study:

• To systematically characterize the clinical, genetic, and pathological features of RMD.
• To investigate the phenotypic spectrum of RMD in Chinese families.
• To correlate CAV3 gene variants with CAV3 protein expression and RMD phenotypes.

Main Methods:

• Clinical data collection from 12 RMD patients across two families.
• Next-generation sequencing and Sanger sequencing for CAV3 gene variant analysis.
• Immunohistochemistry and western blotting to assess CAV3 protein expression.
• Literature review of previously reported RMD cases.

Main Results:

• All 12 patients exhibited childhood-onset exercise intolerance, muscle stiffness, and post-exercise myalgia.
• Percussion-induced muscle mounding and contractions were universally observed.
• A heterozygous c.80G>A (p.Arg27Gln) variant in the CAV3 gene was identified in all patients.
• Reduced CAV3 protein expression was detected in muscle tissue.

Conclusions:

• This study elucidates the clinical, electromyographical, and pathological characteristics of RMD in Chinese families.
• The findings expand the understanding of RMD's variable phenotypes.
• Genetic variants in CAV3 are confirmed as the cause of RMD, impacting protein expression.