Nemaline myopathy is a clinically and genetically heterogeneous condition. The 
clinical spectrum ranges from severe cases with antenatal or neonatal onset and 
early death to late onset cases with only slow progression. Three genes are 
known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 
2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle 
alpha-actin (ACTA1) on chromosome 1q42. We present a 39-year-old lady with a 
mild form of nemaline myopathy, whom we have followed over a period of 25 years. 
She presented at the age of 7 years with symptoms of mild axial and proximal 
muscle weakness. The overall course was essentially static, but at 36 years, she 
went into life-threatening respiratory failure, for which she is currently 
treated with night-time ventilation. Muscle biopsies at 12, 17 and 39 years of 
age showed typical nemaline rods, particularly in type 1 fibres. Areas with 
unevenness of oxidative stain were present in the second and third biopsies. The 
presence of rods and core-like areas was confirmed on electron microscopy. There 
was no detectable alteration in actin expression immunocytochemically. A 
dominant missense mutation in the skeletal muscle alpha-actin gene (ACTA1) was 
found. This case illustrates the clinical and genetic heterogeneity of nemaline 
myopathy, and one phenotype of the wide spectrum of severity caused by mutations 
in the skeletal muscle alpha-actin (ACTA1) gene. In addition, it shows the 
diversity of pathological features that can occur in congenital myopathies due 
to mutations in the same gene.