A novel deep intronic variant in LAMA2 identified by RNA sequencing

Area of Science:

• Genetics
• Molecular Biology
• Neurology

Background:

• LAMA2-related muscular dystrophy results from pathogenic variants in the Laminin alpha2 subunit.
• It presents with high creatine kinase (CK) levels, muscle biopsy abnormalities, merosin deficiency, and central/peripheral nervous system issues.

Observation:

• Genomic and RNA sequencing have uncovered novel non-coding pathogenic variants in LAMA2.
• A deep intronic variant creating a novel splice junction in LAMA2 was identified via RNA sequencing.

Findings:

• The identified variant was homozygous and found in a patient with LAMA2-related muscular dystrophy symptoms.
• Despite the identified variant, merosin staining was retained, suggesting a functional deficit rather than complete absence.

Implications:

• RNA sequencing is crucial for detecting complex variants like deep intronic mutations.
• This finding expands the understanding of LAMA2 pathogenic variants and their diagnostic approaches.
• Retained merosin staining in the presence of a pathogenic variant highlights the complexity of LAMA2-related muscular dystrophy.