Clinical course correlates poorly with muscle pathology in nemaline myopathy

Abstract

Very numerous nemaline bodies, glycogen accumulation, and marked sarcomeric disruption were common in nemaline myopathy associated with mutations in skeletal alpha-actin. Nemaline myopathy due to mutations in alpha-tropomyosin(SLOW) was characterized by preferential rod formation in, and atrophy of, type 1 fibers. Light microscopic features of nemaline myopathy correlate poorly with disease course. Electron microscopy may correlate better with disease severity and genotype.

Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle

“…IF studies revealed that ␤-tubulin was predominantly localized to perimysial connective tissue (Fig. 2 C and D), suggesting that differences observed at the transcriptional level are a molecular correlate of the mildly increased connective tissue often seen in NM muscle (4).…”

“…At the histological level there may be variation in number, size, and location of nemaline rods, the percentage of fast and slow muscle fibers, and the extent of fibrosis. Although muscles from some patients may contain increased proportions of fast (type 2) fibers, predominance of type 1 fibers is a more common feature of NM, and some patients show exclusively type 1 fibers or poor fiber type differentiation (4). Despite our increasing understanding of the genetic basis for NM, it remains unclear how the thin filament defects affect other aspects of muscle function.…”

Sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance

“…Intranuclear rods, which are known to be associated with severe-infantile form of nemaline myopathy with ACTA1 mutation and relatively mild form with MYPN mutation, has been rarely reported [2,4,8,36]. It should be noted that NB per se is not specific although its presence is a mandatory finding of nemaline myopathies.…”

Myopathy mutations in α-skeletal-muscle actin cause a range of molecular defects

“…Studies of actin NEM and AM have provided extensive clinical descriptions of cases and the precise mutations involved (Ryan et al, 2003; Mutations in the gene encoding α-skeletal-muscle actin, ACTA1, cause congenital myopathies of various phenotypes that have been studied since their discovery in 1999. Although much is now known about the clinical aspects of myopathies resulting from over 60 different ACTA1 mutations, we have very little evidence for how mutations alter the behavior of the actin protein and thus lead to disease.…”