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

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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.

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Acknowledgements

The biopsy and autopsy tissue was submitted by Prof. Dr. E.-W. Schwarze, Dortmund, and Dr. Langlitz, Iserlohn, Germany. The SMA gene as a possible underlying cause of the disease was excluded by Prof. Klaus Zerres, Institut für Humangenetik, Universitätsklinikum der RWTH Aachen, Germany. The technical and photographic assistance of Hannelore Mader and Monique Henssen, and the secretarial help of Ingrid Schmitt is gratefully acknowledged. N.L. was supported by the Australian National Health and Medical Research Council: Fellowship 139170 and Project Grant 139039, also by the West Australian Medical and Health Research Infrastructure Fund.

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Correspondence to J. M. Schröder.

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Schröder, J.M., Durling, H. & Laing, N. Actin myopathy with nemaline bodies, intranuclear rods, and a heterozygous mutation in ACTA1 (Asp154Asn). Acta Neuropathol 108, 250–256 (2004). https://doi.org/10.1007/s00401-004-0888-1

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  • DOI: https://doi.org/10.1007/s00401-004-0888-1

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