Our recent work has identified a variable degree of behavioral benefit when treating 2 NM mouse models due to mutations in Acta1 with myostatin inhibition.
The type 1 fiber atrophy and clusters of rods in normal size muscle fibers supported the diagnosis of congenital NM and prompted genetic molecular testing, which led to discovery of the novel ACTA1 variant causative of the myopathy.
We present a series of ACTA1-related cases from a Brazilian cohort of 23 patients with nemaline myopathy, diagnosed after Sanger sequencing the entire coding region of ACTA1, and review the literature on ACTA1-related nemaline myopathy.
Mutations in several NM causal genes have been attributed to the majority of NM cases, particularly mutations in nebulin and skeletal muscle α‑actin 1 (ACTA1), which are responsible for ~70% of cases; therefore, a genetic diagnostic strategy using targeted gene sequencing may potentially improve the diagnosis of suspected NM.
A highly conserved protein, ACTA1 is implicated in multiple muscle diseases, including nemaline myopathy, actin aggregate myopathy, fiber-type disproportion, and rod-core myopathy.
Mutations in ACTA1 have been associated with different pathologic findings including nemaline myopathy, intranuclear rod myopathy, actin myopathy, cap myopathy, congenital fiber type disproportion, and core myopathy.
Multimodal MRI and (31)P-MRS investigations of the ACTA1(Asp286Gly) mouse model of nemaline myopathy provide evidence of impaired in vivo muscle function, altered muscle structure and disturbed energy metabolism.
A de novo dominant mutation in ACTA1 causing congenital nemaline myopathy associated with a milder phenotype: expanding the spectrum of dominant ACTA1 mutations.
This present report describes an infantile onset of nemaline myopathy with a milder clinical course and non-fatal HCM as compared with previous cases, showing clinical diversity in skeletal and cardiac manifestations of conditions associated with ACTA1 mutations.
Mutations in the skeletal muscle actin gene, ACTA1 are responsible for up to 20% of congenital myopathies with a variety of pathologies that includes nemaline myopathy, intranuclear rod myopathy, actin myopathy and congenital fibre type disproportion.In their review of 2003, Sparrow et al. considered how these actin mutations might affect muscle function at the molecular level and thus cause the disease.
Results of muscle biopsies at 7 weeks of age and at 15 months of age from a child with nemaline myopathy due to a novel mutation in the ACTA1 gene are presented.
We raise the possibility that the presence or absence of structural disorganization when mutant actin incorporates into sarcomeres may be an important determinant of whether the histological patterns of CFTD or NM develop in ACTA1 myopathy.