High-Resolution Melting (HRM) Analysis of the Cu/Zn Superoxide Dismutase (SOD1) Gene in Japanese Sporadic Amyotrophic Lateral Sclerosis (SALS) Patients

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, and the majority of ALS are sporadic (SALS). Recently, several causative genes for familial ALS (FALS) were identified, but the cause of the SALS is still unknown. This time, we aimed to identify the genetic background of SALS. First, we applied the new sensitive screening methods: high-resolution melting (HRM) analysis. HRM analysis detected 18 out of 19 known SOD1 gene mutations (94.7% sensitivity). Next, we screened SOD1, three novel mutations (C6Y, Q22H, and S134T) were identified in our own 184 SALS cases (1.63% prevalence), and four mutations in another 255 SALS cases (1.56% prevalence) registered from all over Japan. The patients with SOD1 mutations suggested a relatively young onset and limb involvement at onset. The HRM analysis is a sensitive and easy screening method; we will use this method for screening other ALS causative genes and revealing the genetic background of SALS.

Zinc transporters ZnT3 and ZnT6 are downregulated in the spinal cords of patients with sporadic amyotrophic lateral sclerosis

“…The majority of ALS cases are sporadic; approximately 5-10% of ALS cases are familial (Pasinelli and Brown, 2006). The genetic cause of much of the familial (20%) and part of the sporadic (2%) ALS cases (Akimoto et al, 2011) is mutation in the copper (Cu)/zinc (Zn) superoxide dismutase (SOD1) gene, in which more than 150 different mutations have been identified in ALS patients (Renton et al, 2014). SOD1 (G93A) mutant transgenic (Tg) mice are widely studied as an ALS model (Valentine et al, 2005).…”