Neuropediatrics 2007; 38(6): 282-286
DOI: 10.1055/s-2008-1065356
Original Article

© Georg Thieme Verlag KG Stuttgart · New York

Nemaline Myopathy with Exclusively Intranuclear Rods and a Novel Mutation in ACTA1 (Q139H)

A. Koy 1 , B. Ilkovski 2 , N. Laing 3 , K. North 2 , J. Weis 4 , E. Neuen-Jacob 5 , E. Mayatepek 1 , T. Voit 6
  • 1Department of General Pediatrics, University Children's Hospital, Düsseldorf, Germany
  • 2The Institute of Neuromuscular Research, Faculty of Medicine, The Children's Hospital at Westmead, University of Sydney, Sydney, Australia
  • 3Department of Anatomical Pathology, Centre for Medical Research, University of Western Australia, Perth, Australia
  • 4Department of Neuropathology, RWTH University, Aachen, Germany
  • 5Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
  • 6Institut de Myologie, group Hospitalier de la Pitié Salpêtière, Université Pierre et Marie Curie, Paris, france
Further Information

Publication History

received 07.08.2007

accepted 05.03.2008

Publication Date:
06 May 2008 (online)


Nemaline myopathies (NM) are a rare group of muscle disorders, but represent one of the most common forms of congenital myopathy. The clinical picture ranges from severe muscular hypotonia often leading to death during childhood to mild forms with long life expectancy. Diagnosis is made by muscle biopsy showing characteristic sarcoplasmic and sometimes intranuclear rod bodies. So far, disease-associated mutations have been detected in six genes without any simple correlation between genotype and phenotype or histological findings. We report a patient with a phenotype typical of congenital onset nemaline myopathy and exclusively intranuclear rods. Mutation analysis revealed a new heterozygous missense mutation in exon 3 of the ACTA1 gene (Q139H). Molecular modelling predicts that substitution of Q139 for H139 alters the amino acid side chains and hydrogen bonding which may alter the nucleotide binding cleft by adding ‘bulk’ to the mutated molecule. Two-dimensional gel electrophoresis demonstrates that mutant actin Q139H is expressed at approximately half the level of wild-type actin in the patient's muscle. We speculate that these alterations, although not directly affecting the nuclear export signal, negatively interfere with the nuclear export of the mutated protein and thereby cause retention of mutant actin and intranuclear rod formation.



Dr. med. A. Koy

University Children's Hospital

Moorenstraße 5

40225 Düsseldorf