IBM-type inclusions in a patient with slow-channel syndrome caused by a mutation in the AChR epsilon subunit

Abstract

We report a patient with a slow-channel congenital myasthenic syndrome who carries a novel slow-channel mutation in the ε subunit of the acetylcholine receptor and has tubulofilamentous inclusion bodies, in skeletal muscle of the type observed in hereditary and sporadic inclusion body myositis. Ultrastructural analysis of a muscle specimen obtained at the age of 9 years showed an endplate myopathy typical of the slow-channel syndrome. Twenty years later, a second muscle specimen again showed the endplate myopathy as well numerous nuclear and cytoplasmic tubulofilamentous inclusion bodies. Molecular genetic studies revealed a novel valine to phenylalanine mutation (εV259F) in the M2 domain of the acetylcholine receptor. Coexistence of the slow-channel syndrome with a feature of IBM has not been observed before.