TY - JOUR
T1 - A novel de novo ACTA1 variant in a patient with nemaline myopathy and mitochondrial Complex I deficiency
AU - Pula, Shpresa
AU - Urankar, Kathryn
AU - Norman, Andrew
AU - Pierre, Germaine
AU - Langton-Hewer, Simon
AU - Selby, Victoria
AU - Mason, Faye
AU - Vijayakumar, Kayal
AU - McFarland, Robert
AU - Taylor, Robert W
AU - Majumdar, Anirban
N1 - Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Actins/genetics
KW - Child, Preschool
KW - Electron Transport Complex I/deficiency
KW - Female
KW - Humans
KW - Mitochondrial Diseases/enzymology
KW - Muscle, Skeletal/enzymology
KW - Myopathies, Nemaline/enzymology
U2 - 10.1016/j.nmd.2019.11.014
DO - 10.1016/j.nmd.2019.11.014
M3 - Article (Academic Journal)
C2 - 32005493
SN - 0960-8966
VL - 30
SP - 159
EP - 164
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
IS - 2
ER -