A novel homozygous loss-of-function variant in SOD1 causing progressive spastic tetraplegia and axial hypotonia

Çakar A., Pekbilir E., CEYLANER S., Durmuş H., Battaloğlu E., Şahin U., ...More

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2023 (SCI-Expanded) identifier identifier


SOD1 is the first identified causative gene for amyotrophic lateral sclerosis. Recently, a novel syndrome, presenting with severe childhood-onset spastic tetraplegia and axial hypotonia caused by the homozygous truncating variants in the SOD1 gene, is described. A 22-month-old boy was admitted with a loss of motor functions that began at the age of 9 months. Neurological was significant for axial hypotonia with spastic tetraplegia and hyperekplexia-like jerky movements. In WES, we found a novel homozygous variant (c.52_56del5ins154) in the SOD1 gene, resulting in a total loss of SOD1 mRNA expression in the real-time PCR analysis. Western blot analyses confirmed the lack of protein production. Erythrocyte superoxide dismutase enzymatic activity was nearly abolished. The heterozygous family members displayed reduced superoxide dismutase 1 protein expression and enzymatic activity (by about 40%), compared with the healthy control. Our study expanded the mutation spectrum of SOD1.