Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of typical nemaline rods.
Neuromuscul Disord
; 27(6): 531-536, 2017 Jun.
Article
in En
| MEDLINE
| ID: mdl-28416349
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Inclusion Bodies
/
Actins
/
Myopathies, Nemaline
/
Muscular Diseases
Type of study:
Prognostic_studies
Limits:
Child, preschool
/
Humans
/
Male
Language:
En
Journal:
Neuromuscul Disord
Journal subject:
NEUROLOGIA
Year:
2017
Type:
Article
Affiliation country:
United States