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

Abstract We describe the presentation and follow- up of a three year-old girl with nemaline myopathy (NM) 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. Based on her clinical presentation and histopathological features of NM, 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 NM, although the mechanism remains unclear. Further investigation of this relationship may shed light on the pathogenesis of this entity.