Objectives: To quantify the overall contribution of mutations in the currently known ALS genes in a large cohort of sporadic patients (480 SALS and 48 FALS) and to make genotype–phenotype correlations.
* Mutations in 53 patients, with a cumulative frequency of 11%. 7 novel mutations.
* The highest frequencies of positive cases were obtained in TARDBP (2.7%), C9ORF72 (2.5%), and SOD1 (2.1%).
* Mutated patients was indistinguishable from that without mutations as no significant differences were observed with regard to age and site of onset, frequency of clinical phenotypes, and survival.
* However, by separately evaluating genotype–phenotype correlation in single genes, clinical differences were observed among different genes.
** Duration of disease was significantly shorter in patients harboring the C9ORF72 expansion and longer in the SOD1 group.
** A high frequency of predominant upper motor neuron phenotype was observed among patients with TARDBP mutations.
** Two patients, 1 with C9ORF72 and 1 with SOD1 mutation, had concurrent ANG mutations.
** Mutations were detected in 43.7% of patients with FALS.