Mutations and polymorphisms of the skeletal muscle α‐actin gene (ACTA1) |
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| Authors: | Nigel G Laing Danielle E Dye Carina Wallgren‐Pettersson Gabriele Richard Nicole Monnier Suzanne Lillis Thomas L Winder Hanns Lochmüller Claudio Graziano Stella Mitrani‐Rosenbaum Darren Twomey John C Sparrow Alan H Beggs Kristen J Nowak |
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| Institution: | 1. Centre for Medical Research, University of Western Australia, Western Australian Institute for Medical Research, QEII Medical Centre, Nedlands, Western Australia, Australia;2. Department of Medical Genetics, University of Helsinki and the Folkh?lsan Insitute of Genetics, Helsinki, Finland;3. GeneDx, Gaithersburg, Maryland;4. Laboratoire de Biochimie et Génétique Moléculaire, INSERM U607, Centre Hospitalier Universitaire de Grenoble, Grenoble, France;5. DNA Laboratory, Guy's Hospital, London, England, United Kingdom;6. Prevention Genetics, Marshfield, Wisconsin;7. Institute of Human Genetics, University of Newcastle, Newcastle upon Tyne, United Kingdom;8. Medical Genetics Unit, Policlinico S. Orsola‐Malpighi, Bologna, Italy;9. Goldyne Savad Institute of Gene Therapy, Hadassa–The Hebrew University Medical Center, Jerusalem, Israel;10. Department of Biology (Area 10), University of York, York, United Kingdom;11. Genomics Program and Division of Genetics, The Manton Center for Orphan Disease Research, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts |
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| Abstract: | The ACTA1 gene encodes skeletal muscle α‐actin, which is the predominant actin isoform in the sarcomeric thin filaments of adult skeletal muscle, and essential, along with myosin, for muscle contraction. ACTA1 disease‐causing mutations were first described in 1999, when a total of 15 mutations were known. In this article we describe 177 different disease‐causing ACTA1 mutations, including 85 that have not been described before. ACTA1 mutations result in five overlapping congenital myopathies: nemaline myopathy; intranuclear rod myopathy; actin filament aggregate myopathy; congenital fiber type disproportion; and myopathy with core‐like areas. Mixtures of these histopathological phenotypes may be seen in a single biopsy from one patient. Irrespective of the histopathology, the disease is frequently clinically severe, with many patients dying within the first year of life. Most mutations are dominant and most patients have de novo mutations not present in the peripheral blood DNA of either parent. Only 10% of mutations are recessive and they are genetic or functional null mutations. To aid molecular diagnosis and establishing genotype–phenotype correlations, we have developed a locus‐specific database for ACTA1 variations ( http://waimr.uwa.edu.au ). Hum Mutat 30:1–11, 2009. © 2009 Wiley‐Liss, Inc. |
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| Keywords: | skeletal muscle α ‐actin ACTA1 congenital myopathies locus‐specific database |
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