A novel lamin A/C gene mutation causing spinal muscular atrophy phenotype with cardiac involvement: report of one...

Area of Science:

• Genetics
• Neurology
• Cardiology

Background:

• Mutations in the lamin A/C gene are linked to various diseases, termed laminopathies, including muscular dystrophies and cardiomyopathies.
• While rare, a connection between lamin A/C mutations and spinal muscular atrophy (SMA) with cardiomyopathy has been suggested but not firmly established.

Observation:

• A 65-year-old Japanese male presented with lower limb amyotrophy, gait disturbance since childhood, and cardiac dysfunction.
• Neurological and electrophysiological evaluations indicated spinal muscular atrophy type 3.
• Genetic analysis revealed a novel nonsense mutation (p.Q353X) in the lamin A/C gene in the patient and his family, who also exhibited cardiac conditions like atrioventricular block.

Findings:

• This case represents the first documented instance of a spinal muscular atrophy phenotype associated with a lamin A/C gene mutation in a Japanese individual.
• The identified mutation, p.Q353X, provides further evidence for the role of lamin A/C gene defects in SMA.

Implications:

• The findings suggest that lamin A/C gene analysis should be considered in patients presenting with an SMA phenotype, particularly when accompanied by unexplained cardiac disease and a positive family history.
• This broadens the diagnostic considerations for laminopathies and emphasizes the genotype-phenotype correlation within these genetic disorders.