Acta Neuropathologica

, Volume 108, Issue 3, pp 250–256

Actin myopathy with nemaline bodies, intranuclear rods, and a heterozygous mutation in ACTA1 (Asp154Asn)

Case Report

DOI: 10.1007/s00401-004-0888-1

Cite this article as:
Schröder, J.M., Durling, H. & Laing, N. Acta Neuropathol (2004) 108: 250. doi:10.1007/s00401-004-0888-1

Abstract

Mutations in the skeletal muscle α-actin gene (ACTA1) are associated by and large with three muscle diseases (1) congenital actin myopathy, (2) nemaline myopathy, and (3) intranuclear rod myopathy. More than 70 mutations have now been identified. The majority of ACTA1 mutations are dominant, a small number are recessive and most isolated cases with no previous family history have de novo dominant mutations. The present case, a boy of healthy Turkish parents, had a severe form of the disease of the latter type due to a heterozygous, presumably de novo mutation of the ACTA1 gene in exon 4 (Asp154Asn), with lack of spontaneous movements at birth requiring immediate mechanical ventilation. He died at the age of 9 weeks due to respiratory failure, secondary pneumonia, and chylothorax. The biopsy specimen of the femoral muscle was characterized by pleomorphic alterations with numerous muscle fibers showing accumulation of actin filaments, but, in addition, both nemaline bodies and intranuclear rod bodies. This was also seen in several other muscles investigated at autopsy. No developmental abnormalities of the central nervous system, and no loss of spinal motor neurons were detected despite atrophy or hypotrophy of a considerable number of muscle fibers. The peripheral nervous system, which has not been studied before in patients with ACTA1 mutations, showed no loss of motor or sensory myelinated fibers and no loss of sensory neurons in spinal ganglia.

Keywords

ACTA1 mutationCongenital actin myopathyNemaline bodiesIntranuclear rod bodies

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Department of Neuropathology, University HospitalRWTHAachenGermany
  2. 2.Neurogenetic Laboratory, Department of Anatomical PathologyRoyal Perth HospitalPerthAustralia
  3. 3.Centre for Neuromuscular and Neurological Disorders, Australian Neuromuscular Research Institute, and Centre for Medical Research, University of Western Australia, West Australian Institute for Medical ResearchQEII Medical CentreNedlandsAustralia