A novel de novo ACTA1 variant in a patient with nemaline myopathy and mitochondrial Complex I deficiency

Neuromuscul Disord. 2020 Feb;30(2):159-164. doi: 10.1016/j.nmd.2019.11.014. Epub 2019 Dec 1.

Abstract

We describe the presentation and follow-up of a three-year-old girl with nemaline myopathy due to a de-novo variant in ACTA1 (encoding skeletal alpha actin) and moderately low enzyme level of Complex I of the mitochondrial respiratory chain. She presented in the neonatal period with hypotonia, followed by weakness in the facial, bulbar, respiratory and neck flexors muscles. A biopsy of her quadriceps muscle at the age of one year showed nemaline rods. Based on her clinical presentation of a congenital myopathy and histopathological features on a muscle biopsy, ACTA1 was sequenced, and this revealed a novel sequence variant, c.760 A>C p. (Asn254His). In addition, mitochondrial respiratory chain enzymatic activity of skeletal muscle biopsy showed a moderately low activity of complex I (nicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase). Disturbances of Complex I of the respiratory chain have been reported in patients with nemaline myopathy, although the mechanism remains unclear.

Keywords: ACTA1; Mitochondrial dysfunction; Nemaline myopathy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics*
  • Child, Preschool
  • Electron Transport Complex I / deficiency*
  • Electron Transport Complex I / genetics
  • Female
  • Humans
  • Mitochondrial Diseases / enzymology
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology
  • Myopathies, Nemaline / enzymology
  • Myopathies, Nemaline / genetics*
  • Myopathies, Nemaline / pathology

Substances

  • ACTA1 protein, human
  • Actins
  • Electron Transport Complex I

Supplementary concepts

  • Mitochondrial complex I deficiency