Prevalence of SOD1 mutations in the Italian ALS population.

Background: Five to 10% of amyotrophic lateral sclerosis (ALS) cases are reported to be familial (FALS), and mutations of SOD1 account for 20% of these cases. However, estimates of SOD1 mutation prevalence have been exclusively based on case series and clinic referral cohorts.
Objective: To assess the frequency and nature of SOD1 mutations in a large population-based cohort of Italian patients diagnosed with ALS over a 6-year period.
Methods: All ALS cases incident in Piemonte and Valle d'Aosta, Italy, are collected through a prospective epidemiologic register. Almost all patients with ALS resident in the largest province of Piemonte (Turin) have been evaluated for SOD1 mutations in the 6-year period 2000 through 2005.
Results: During the study period, 386 residents of Turin province were diagnosed with ALS (mean crude incidence rate of 2.9/100,000/year). Twenty-two patients (5.7%) had a positive family history of ALS. SOD1 analysis was performed in 325 patients (84.2% of the whole cohort), including all FALS cases. Five patients carried a SOD1 coding mutation, three with a family history of ALS (13.6% of FALS) and two in sporadic cases (0.7% of sporadic ALS).
Conclusions: In this population-based series, the frequency of familial amyotrophic lateral sclerosis (FALS) was lower than that reported in series from ALS referral centers. While the frequency of SOD1 mutations in FALS was similar to the data reported in the literature, only 0.7% of sporadic ALS cases had a SOD1 mutation. Our data indicate that studies from referral centers may overestimate the frequency of FALS and of SOD1 mutations in sporadic ALS.