Amyotrophic lateral sclerosis patients with optineurin gene variants: A case series

Abstract

Background & Objective: Amyotrophic lateral sclerosis (ALS) is an incurable and fatal disease that affects motor neurons, and can be sporadic or familial. Pathogenic variants in the optineurin gene (OPTN) have been implicated in the pathogenesis of ALS, type 12 (ALS12). Knowledge of the causative/disease-modifying genes may provide a novel target for gene therapy.

Methods: We present three patients with ALS who were followed up at our neuromuscular outpatient clinic, and underwent clinical, neurophysiological, neuropsychological, radiological, laboratory, and genetic investigations. We identified variants by analyzing the entire exome and adjacent intronic regions of the causative genes.

Results: The patients had c.1078_1079del, p.Lys360Valfs*18 and c.1242+1G>A homozygous variants and c.403G>T, p.Glu135* heterozygous variant in OPTN, and presented with different clinical features.

Conclusions: Clinicians should be aware of the phenotypes and genetic profiles of patients to gain a better understanding of ALS12 and contribute to the development of new therapies.