title: A de novo dominant mutation in ACTA1 causing congenital nemaline myopathy associated with a milder phenotype: expanding the spectrum of dominant ACTA1 mutations.
abstract: We describe the presentation and six-year follow up of a child with nemaline myopathy due to a de novo mutation in the skeletal muscle α-actin gene (ACTA1) characterized by dramatic improvement during the early childhood years. The presentation in this female patient was infantile-onset weakness in the facial, bulbar, respiratory and neck flexor muscles. A six-year follow-up revealed continued progressive improvement in her muscle strength. Based upon the histopathologic and ultrastructural features of nemaline rod disease, ACTA1 was sequenced. This revealed a mutation in exon 4 of ACTA1 (c.557A>G). Our report further expands the phenotypic spectrum associated with ACTA1 mutations. Although it is difficult to infer any genotype-phenotype correlation, this report stimulates the discussion regarding the pathophysiologic mechanism of the clinical improvement seen in some patients with ACTA1 mutations.
authors.affiliation: Genetics and Metabolism Program, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Levesque
authors.forename: M R
authors.initials: MR
authors.lastname: Del Bigio
authors.forename: S
authors.initials: S
authors.lastname: Krawitz
authors.forename: A A
authors.initials: AA
authors.lastname: Mhanni
mesh_terms: D000199:Actins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D017696:Myopathies, Nemaline / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D000199:Actins