title: Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine.
abstract: Variants in ACTA1, which encodes α-skeletal actin, cause several congenital myopathies, most commonly nemaline myopathy. Autosomal recessive variants comprise approximately 10% of ACTA1 myopathy. All recessive variants reported to date have resulted in loss of skeletal α-actin expression from muscle and severe weakness from birth. Targeted next-generation sequencing in two brothers with congenital muscular dystrophy with rigid spine revealed homozygous missense variants in ACTA1. Skeletal α-actin expression was preserved in these patients. This report expands the clinical and histological phenotype of ACTA1 disease to include congenital muscular dystrophy with rigid spine and dystrophic features on muscle biopsy. This represents a new class of recessive ACTA1 variants, which do not abolish protein expression.
authors.affiliation: 1] Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia [2] Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Gina L
authors.initials: GL
authors.lastname: O'Grady
authors.affiliation: 1] Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia [2] Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Best
authors.affiliation: 1] Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia [2] Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Oates
authors.affiliation: Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Simranpreet
authors.initials: S
authors.lastname: Kaur
authors.affiliation: Histopathology Department, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Charlton
authors.affiliation: Electron Microscope Unit, Concord Repatriation General Hospital, Sydney, New South Wales, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Brammah
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Punetha
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Akanchha
authors.initials: A
authors.lastname: Kesari
authors.affiliation: 1] Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia [2] Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia [3] Murdoch Childrens Research Institute, Melbourne, Victoria, Australia [4] Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: North
authors.affiliation: 1] Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia [2] Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Ilkovski
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.affiliation: 1] Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia [2] Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Nigel F
authors.initials: NF
authors.lastname: Clarke
mesh_terms: D000199:Actins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000595:Amino Acid Sequence; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D020914:Myopathies, Structural, Congenital / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D013131:Spine / Q000473:pathology*
chemical_list: D000199:Actins