ANO5-muscular dystrophy: clinical, pathological and molecular findings

Area of Science:

• Genetics
• Neurology
• Cardiology

Background:

• Anoctamin 5 (ANO5) encodes a calcium-activated chloride channel.
• Recessive ANO5 mutations cause skeletal muscle disorders resembling dysferlinopathy.
• ANO5-related muscular dystrophies share similarities with dysferlinopathies caused by DYSF gene mutations.

Purpose of the Study:

• To investigate the phenotype and genotype of patients with ANO5-related muscular dystrophy.
• To explore the association between ANO5 mutations, amyloid deposition, and cardiac involvement.
• To characterize novel ANO5 mutations and genetic variations.

Main Methods:

• Phenotypic and genotypic analysis of seven unrelated patients with ANO5-muscular dystrophy.
• Amyloid subtyping using laser capture microdissection and mass spectrometry-based proteomics.
• Detailed clinical assessment including cardiac evaluation and electrophysiological studies.

Main Results:

• Three patients exhibited muscle amyloid deposition; two had cardiac involvement.
• One patient without skeletal muscle amyloidosis showed cardiac involvement with septal hypokinesis and supraventricular tachycardia.
• Amyloid deposits did not contain ANO5 protein but other known amyloidogenic proteins.
• Three patients presented with myotonic discharges without clinical myotonia.
• Four novel ANO5 mutations were identified, including a large deletion of the entire ANO5 gene.

Conclusions:

• ANO5 mutations may be linked to muscle amyloid deposition, though the nature and cause of amyloidosis are indeterminate.
• The relationship between ANO5 mutations, amyloid deposition, and cardiac involvement requires further investigation.
• ANO5 gene analysis is recommended for unexplained muscle amyloid deposition.
• Electrical myotonia can be a feature of ANO5-related muscular dystrophy.