Fetal akinesia caused by a novel actin filament aggregate myopathy skeletal muscle actin gene (ACTA1) mutation

Stenzel, Werner; Prokop, Stefan; Kress, Wolfram; Huppmann, Stephanie; Loui, Andrea; Sarioglu, Nanette M.E.; Laing, Nigel G.; Sparrow, John C.; Heppner, Frank L.; Goebel, Hans H.

doi:10.1016/j.nmd.2010.06.008

« Previous Next »Neuromuscular Disorders
Volume 20, Issue 8 , Pages 531-533, August 2010

Fetal akinesia caused by a novel actin filament aggregate myopathy skeletal muscle actin gene (ACTA1) mutation

Werner Stenzel
- Institute of Neuropathology, Charité University Medicine, Berlin, Germany
- Corresponding author. Address: Department of Neuropathology, Charité – Universitätsmedizin Berlin, Charité Campus Mitte – Virchowweg 15, Charitéplatz 1, D-10117 Berlin, Germany. Tel.: +49 (0)30 450 536 073; fax: +49 (0)30 450 536 940.
Stefan Prokop
- Institute of Neuropathology, Charité University Medicine, Berlin, Germany
Wolfram Kress
- Department of Human Genetics, Würzburg, Germany
Stephanie Huppmann
- Department of Neonatology, Charité University Medicine, Berlin, Germany
Andrea Loui
- Department of Neonatology, Charité University Medicine, Berlin, Germany
Nanette M.E. Sarioglu
- Institute of Pathology and Placentology, Charité University Medicine, Berlin, Germany
Nigel G. Laing
- Center for Medical Research, University of Western Australia M519, Western Australian Institute for Medical Research, Nedlands, Western Australia, Australia
John C. Sparrow
- Department of Biology (Area 10), University of York, York YO10 5DD, UK
Frank L. Heppner
- Institute of Neuropathology, Charité University Medicine, Berlin, Germany
Hans H. Goebel
- Institute of Neuropathology, Charité University Medicine, Berlin, Germany
- Department of Neuropathology, University Medicine, Johannes Gutenberg University, Mainz, Germany

Received 23 March 2010; received in revised form 27 May 2010; accepted 15 June 2010.

Abstract

We report a female newborn, diagnosed with fetal akinesia in utero, who died one hour after birth. Post-mortem muscle biopsy demonstrated actin-filament myopathy based on immunolabelling for sarcomeric actin, and large areas of filaments, without rod formation, ultrastructurally. Analysis of DNA extracted from the muscle disclosed a novel de novo heterozygous c.44G>A, GGC>GAC, ‘p.Gly15Asp’ mutation in the ACTA1 gene. Analysis of the location of the mutated amino-acid in the actin molecule suggests the mutation most likely causes abnormal nucleotide binding, and consequent pathological actin polymerization. This case emphasizes the association of fetal akinesia with actin-filament myopathy.

Keywords: ACTA1, Nemaline myopathy, Actin filament aggregate myopathy, Fetal akinesia sequence