A Novel Variant in Superoxide Dismutase 1 Gene (p.V119M) in Als Patients with Pure Lower Motor Neuron Presentation.

Claudia Ricci,Stefania Battistini,Fabio Giannini,Stefania Casali,Silvia Bocci,Giulia Riolo

doi:10.3390/genes12101544

Claudia Ricci, Stefania Battistini + Show 4 more

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https://doi.org/10.3390/genes12101544

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Journal: Genes	Publication Date: Sep 29, 2021
Citations: 3	License type: CC BY 4.0

Affiliation: University of Siena

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disorder characterized by degeneration of motor neurons in the cerebral cortex, brain stem, and spinal cord. Most cases of ALS appear sporadically, but 5–10% of patients have a family history of disease. Mutations in the superoxide dismutase 1 gene (SOD1) have been found in 12–23% of familial cases and in 1–2% of sporadic cases. Currently, more than 180 different SOD1 gene variants have been identified in ALS patients. Here, we describe two apparently sporadic ALS patients carrying the same SOD1 c.355G>A variant, leading to the p.V119M substitution, not previously described. Both the patients showed pure lower motor neuron phenotype. The former presented with the flail leg syndrome, a rare ALS variant, characterized by progressive distal onset weakness and atrophy of lower limbs, slow progression and better survival than typical ALS. The latter exhibited rapidly progressive weakness of upper and lower limbs, neither upper motor neuron nor bulbar involvement, and shorter survival than typical ALS. We provide an accurate description of the phenotype, and a bioinformatics analysis of the p.V119M variant on protein structure. This study may increase the knowledge about genotype-phenotype correlations in ALS and improve the approach to ALS patients.

Highlights

Amyotrophic Lateral Sclerosis (ALS) is an adult-onset, progressive and fatal neurodegenerative disease characterized by the degeneration of the motor neurons in the brain and spinal cord, resulting in progressive weakness of bulbar, thoracic, abdominal and limb muscles
Motor evoked potential (MEP) examination showed the sparing of central motor pathways
The identification of the novel p.V119M variant in the superoxide dismutase 1 gene (SOD1) gene in two patients with pure lower motor neuron syndrome expands the spectrum of ALS phenotypes associated with SOD1 mutations

Summary

Introduction

Amyotrophic Lateral Sclerosis (ALS) is an adult-onset, progressive and fatal neurodegenerative disease characterized by the degeneration of the motor neurons in the brain and spinal cord, resulting in progressive weakness of bulbar, thoracic, abdominal and limb muscles. Most affected individuals show spinal onset, characterized by focal limb weakness initiating in a distinct region of the body and propagating from this area to secondary sites [3]. Most cases become generalized and show combinations of both LMN and UMN signs affecting spinal and brainstem regions [4]. Other brain functions, such as oculomotor and sphincter functions, are rarely involved. Cognitive impairements may precede or occur after the onset of motor symptoms.

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