Since the patients are characterized by generalized muscle weakness together with neurodevelopmental phenotypes, it is suggested that NEB mutations could manifest more diverse phenotypes than those previously described.
Recessive nebulin (NEB) mutations are a common cause of nemaline myopathy (NM), typically characterized by generalized weakness of early-onset and nemaline rods on muscle biopsy.
This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved.
This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved.
Protein expression studies in nine cases suggested a correlation between specific mutations, RyR1 protein levels and resulting phenotype: in particular, whilst patients with dominant or recessive mutations associated with typical CCD phenotypes appeared to have normal RyR1 expression, individuals with more generalized weakness, multi-minicores and external ophthalmoplegia had a pronounced depletion of the RyR1 protein.