Journal article
Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of typical nemaline rods
Neuromuscular disorders : NMD, Vol.27(6), pp.531-536
06/2017
DOI: 10.1016/j.nmd.2017.02.012
PMCID: PMC5918412
PMID: 28416349
Abstract
•ACTA1-myopathy can present with cytoplasmic bodies in the absence of nemaline rods.•p.Asn94Lys ACTA1 mutation may be linked to this pathology and severe phenotype.•ACTA1 mosaicism may masquerade as recessive inheritance, complicating the workup.
Mutations in ACTA1 cause a group of myopathies with expanding clinical and histopathological heterogeneity. We describe three patients with severe ACTA1-related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline rods. Patient 1 is a five-year-old boy who presented at birth with severe weakness and respiratory failure, requiring mechanical ventilation. Whole exome sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation. Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory insufficiency at birth requiring mechanical ventilation. Both died at 6 months of age. The same heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation was identified by whole exome sequencing. We conclude that clinically severe ACTA1-related myopathy can present with muscle morphological findings suggestive of cytoplasmic body myopathy in the absence of definite nemaline rods. The Asn94Lys mutation in skeletal muscle sarcomeric α-actin may be linked to this histological appearance. These novel ACTA1 cases also illustrate the successful application of whole exome sequencing in directly arriving at a candidate genetic diagnosis in patients with unexpected phenotypic and histologic features for a known neuromuscular gene.
Details
- Title: Subtitle
- Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of typical nemaline rods
- Creators
- Sandra Donkervoort - National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USASophelia H.S Chan - Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SARLeslie H Hayes - National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USANathaniel Bradley - National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USADavid Nguyen - National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USAMeganne E Leach - National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USAPayam Mohassel - National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USAYing Hu - National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USAMathula Thangarajh - Children's National Health System, Washington, DC, USADiana Bharucha-Goebel - National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USAAmanda Kan - Department of Pathology and Clinical Biochemistry, The Queen Mary Hospital, Hong Kong SARRonnie S.L Ho - Department of Pathology and Clinical Biochemistry, The Queen Mary Hospital, Hong Kong SARChristine A Reyes - Children's National Health System, Washington, DC, USAJessica Nance - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USASteven A Moore - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USAA. Reghan Foley - National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USACarsten G Bönnemann - National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA
- Resource Type
- Journal article
- Publication Details
- Neuromuscular disorders : NMD, Vol.27(6), pp.531-536
- DOI
- 10.1016/j.nmd.2017.02.012
- PMID
- 28416349
- PMCID
- PMC5918412
- NLM abbreviation
- Neuromuscul Disord
- ISSN
- 0960-8966
- eISSN
- 1873-2364
- Publisher
- Elsevier B.V
- Grant note
- DOI: 10.13039/100000002, name: NIH; DOI: 10.13039/100000065, name: NINDS; name: Iowa Wellstone Muscular Dystrophy Cooperative Research Center, award: NS053672
- Language
- English
- Date published
- 06/2017
- Academic Unit
- Pathology
- Record Identifier
- 9984047658902771
Metrics
12 Record Views