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

2019; Elsevier BV; Volume: 30; Issue: 2 Linguagem: Inglês

10.1016/j.nmd.2019.11.014

1873-2364

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

Genetic Neurodegenerative Diseases

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.