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Neuromuscul Disord. 2017 Jun;27(6):531-536. doi: 10.1016/j.nmd.2017.02.012. Epub 2017 Mar 2.

Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of typical nemaline rods.

Author information

1
National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA.
2
Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR.
3
National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA; Boston Children's Hospital, Boston, MA, USA.
4
National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA; Children's National Health System, Washington, DC, USA.
5
Children's National Health System, Washington, DC, USA.
6
Department of Pathology and Clinical Biochemistry, The Queen Mary Hospital, Hong Kong SAR.
7
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
8
Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
9
National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA. Electronic address: carsten.bonnemann@nih.gov.

Abstract

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.

KEYWORDS:

ACTA1; Congenital myopathies; Cytoplasmic bodies; Skeletal muscle α-actin

PMID:
28416349
PMCID:
PMC5918412
DOI:
10.1016/j.nmd.2017.02.012
[Indexed for MEDLINE]
Free PMC Article

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