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Updated: Apr 16, 2026
Analysis of Embryonic and Larval Zebrafish Skeletal Myofibers from Dissociated Preparations
Published on: November 13, 2013
Zebra body myopathy is caused by a mutation in the skeletal muscle actin gene (ACTA1)
C A Sewry1, J L Holton2, D J Dick3
1Dubowitz Neuromuscular Centre, UCL Institute of Child Health and Great Ormond Street Hospital for Children, London, UK; Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, UK.
Abstract:
We present follow up data on the original case of 'zebra body myopathy' published by Lake and Wilson in 1975. Pathological features in a second biopsy performed at the age of 29 years included a wide variation in fibre size, multiple split fibres, excess internal nuclei and endomysial connective tissue, rimmed vacuoles, accumulation of myofibrillar material and large 'wiped out' areas lacking stain for oxidative enzymes. The presence of nemaline rods and actin-like filaments in addition to small zebra bodies suggested ACTA1 as a candidate gene. This has been confirmed by the identification of a novel c.1043T.p.Leu348Gln mutation, which probably occurred de novo. This case illustrates that the myopathy associated with zebra bodies is part of the spectrum of myopathies associated with the ACTA1 gene. It also highlights that accumulation of actin filaments is not confined to severe neonatal ACTA1 cases and that progression of weakness can occur in congenital myopathies, as the patient is now wheelchair bound and can only stand with the aid of a walking frame.
Insights
This study identifies a new mutation in the ACTA1 gene in a patient with zebra body myopathy, confirming it as part of the ACTA1-related myopathy spectrum. The findings show that actin accumulation can occur in non-neonatal cases, with potential disease progression.
Area of Science:
- Neurology
- Genetics
- Pathology
Background:
- Follow-up study of the original 'zebra body myopathy' case from 1975.
- Investigates pathological features in a second biopsy at age 29.
Observation:
- Second biopsy revealed significant fiber size variation, split fibers, internal nuclei, and endomysial fibrosis.
- Observed rimmed vacuoles, myofibrillar material accumulation, and enzyme-deficient areas.
- Presence of nemaline rods, actin-like filaments, and small zebra bodies noted.
Findings:
- Identified a novel de novo ACTA1 gene mutation (c.1043T>p.Leu348Gln).
- Confirmed ACTA1 as the causative gene for this form of zebra body myopathy.
- Demonstrated that actin filament accumulation is not limited to severe neonatal ACTA1 myopathies.
Implications:
- Zebra body myopathy is now recognized as part of the ACTA1 gene-related myopathy spectrum.
- Highlights the potential for progressive weakness in congenital myopathies.
- Suggests ACTA1 mutations should be considered in congenital myopathies with progressive weakness and specific pathological findings.
