ABSTRACT
Nemaline myopathy is a clinically heterogeneous congenital myopathy caused by mutations in at least 6 genes related to thin filaments. Histologically, they show a characteristic if not homogeneous picture of nemaline rods, essential for the diagnosis. However, little is known regarding the development and progression of muscle histopathologic changes in nemaline myopathy. Results of muscle biopsies at 7 weeks of age and at 15 months of age from a child with nemaline myopathy due to a novel mutation in the ACTA1 gene are presented. The findings of the biopsies, separated by 13 months, demonstrate progression from vague cytoplasmic bodies in the first biopsy to typical nemaline rods in the second biopsy.
Subject(s)
Actins/genetics , Muscle, Skeletal/diagnostic imaging , Myopathies, Nemaline/genetics , Actins/metabolism , Biopsy/methods , Follow-Up Studies , Humans , Infant , Male , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Myopathies, Nemaline/diagnosis , Myopathies, Nemaline/metabolism , Myopathies, Nemaline/ultrastructure , UltrasonographyABSTRACT
We describe an atypical case of nemaline myopathy with an unusual distribution of muscle weakness who presented at 14 years of age with kyphoscoliosis. In this patient, we demonstrate heterozygosity for a de novo CGT-CAT (Arg167His) mutation in a constitutively expressed exon (exon 5) of slow alpha-tropomyosin (TPM3). This is the first mutation identified in a constitutively expressed exon of TPM3 in a nemaline myopathy patient, but is similar to recently described mutations in beta-tropomyosin (TPM2) associated with nemaline myopathy and mutations in fast alpha-tropomyosin (TPM1) which cause hypertrophic cardiomyopathy.
Subject(s)
Drosophila Proteins , Myopathies, Nemaline/genetics , Tropomyosin/genetics , Adenosine Triphosphatases/metabolism , Adolescent , Arginine/genetics , DNA Mutational Analysis , Exons , Female , Genetic Carrier Screening , Histidine/genetics , Humans , Muscle Fibers, Skeletal/enzymology , Muscle Fibers, Skeletal/pathology , Muscle Fibers, Skeletal/ultrastructure , Muscle Weakness/etiology , Muscle Weakness/genetics , Mutation, Missense , Myopathies, Nemaline/physiopathology , Myopathies, Nemaline/ultrastructureABSTRACT
A sporadic case of congenital myopathy had severe muscle weakness of neonatal onset. Nemaline and cytoplasmic bodies were detected in muscle biopsies taken at 4 months of age. These findings were consistent with a diagnosis of nemaline myopathy (severe neonatal form). The simultaneous and abundant presence of these two types of sarcoplasmic inclusion has been found in only a few cases. However, these cases suggest that the sarcoplasmic inclusions may be formed, at least partially, by common mechanisms.
