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

Shpresa Pula, Kathryn Urankar, Andrew Norman, Germaine Pierre, Simon Langton-Hewer, Victoria Selby, Faye Mason, Kayal Vijayakumar, Robert McFarland, Robert W Taylor, Anirban Majumdar

Research output: Contribution to journalArticle (Academic Journal)peer-review

5 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)159-164
Number of pages6
JournalNeuromuscular Disorders
Issue number2
Publication statusPublished - Feb 2020


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


Dive into the research topics of 'A novel de novo ACTA1 variant in a patient with nemaline myopathy and mitochondrial Complex I deficiency'. Together they form a unique fingerprint.

Cite this