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

Autor: Donkervoort S; National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA., Chan SHS; Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR., Hayes LH; National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA; Boston Children's Hospital, Boston, MA, USA., Bradley N; National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA., Nguyen D; National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA., Leach ME; National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA; Children's National Health System, Washington, DC, USA., Mohassel P; National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA., Hu Y; National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA., Thangarajh M; Children's National Health System, Washington, DC, USA., Bharucha-Goebel D; National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA; Children's National Health System, Washington, DC, USA., Kan A; Department of Pathology and Clinical Biochemistry, The Queen Mary Hospital, Hong Kong SAR., Ho RSL; Department of Pathology and Clinical Biochemistry, The Queen Mary Hospital, Hong Kong SAR., Reyes CA; Children's National Health System, Washington, DC, USA., Nance J; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Moore SA; Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA., Foley AR; National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA., Bönnemann CG; National Institutes of Health, Neuromuscular and Neurogenetic Disorders of Childhood Section, Bethesda, MD, USA. Electronic address: carsten.bonnemann@nih.gov.
Jazyk: angličtina
Zdroj: Neuromuscular disorders : NMD [Neuromuscul Disord] 2017 Jun; Vol. 27 (6), pp. 531-536. Date of Electronic Publication: 2017 Mar 02.
DOI: 10.1016/j.nmd.2017.02.012
Abstrakt: 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.
(Copyright © 2017. Published by Elsevier B.V.)
Databáze: MEDLINE
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