Severe nemaline myopathy associated with consecutive mutations E74D and H75Y on a single ACTA1 allele

Muscle biopsy revealed severely atrophic and rounded muscle fibers with considerable variation in diameter and pronounced disorganization of the myofibers. Electron microscopy indicated a distinct disturbance of the myofibrillar architecture and nemaline rods. In view of previously described cases carrying different single missense mutations of the amino acid residues E74 or H75, we suggest that the particular genotype E74D/H75Y is compatible with the severity of the patient's phenotype. The possibility of germ cell mosaicism should be taken into account in genetic counseling.