MYH2-associated myopathy caused by a novel splice-site variant

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• MYH2 gene encodes MyHCIIa, crucial for fast type 2A muscle fibers.
• Pathogenic variants in MYH2 are linked to dominant and recessive myopathies.
• Understanding MYH2-related disorders is vital for diagnosis and treatment.

Observation:

• A family presented with a slowly progressive, predominantly proximal myopathy across four generations.
• Affected individuals lacked typical MYH2-associated myopathy features like contractures and ophthalmoplegia.
• A novel MYH2 variant (c.5673+1G>C) was identified and segregated with the disease.

Findings:

• The identified MYH2 variant affects RNA splicing, generating aberrant transcripts.
• Muscle biopsy findings in the proband supported the variant's pathogenicity.
• This novel variant is causative of the observed autosomal dominant myopathy.

Implications:

• This study expands the clinical and molecular understanding of MYH2-associated myopathies.
• The findings highlight the importance of genetic analysis in atypical myopathy presentations.
• Further research into MYH2 splicing defects may reveal new therapeutic targets.