Novel TUBA4A variant causes congenital myopathy with focal myofibrillar disorganisation

BACKGROUND: variant in two unrelated Chinese patients with sporadic congenital myopathy. METHODS: variant. RESULTS: (NM_006000), encoding tubulin alpha-4A, in two unrelated patients with clinicopathologically diagnosed sporadic congenital myopathy. The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiquitin-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of the L227F mutant TUBA4A resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model. CONCLUSION: as well as tubulinopathies, and added a new type of congenital myopathy to be taken into consideration in the differential diagnosis.