SMN1 gene, but not SMN2, is a risk factor for sporadic ALS

SMN1 gene deletions cause spinal muscular atrophy, and SMN2 gene deletions have been associated with sporadic lower motor neuron diseases. To study the frequency of abnormal SMN1 gene copy numbers and to determine whether SMN2 gene modulates the risk of amyotrophic lateral sclerosis (ALS) or the duration of evolution. The authors studied SMN1 and SMN2 genes in 600 patients with sporadic ALS and 621 controls using a quantitative PCR method. The authors found an association of ALS with an abnormal copy number (one or three copies) of SMN1 gene (p < 0.0001) with an OR of 2.8 (1.8 to 4.4, 95% CI). There was no association with SMN2 copy numbers and no effect of SMN2 copies on the duration of evolution in ALS independently of SMN1 copy number. Abnormal SMN1 gene copy numbers are a genetic risk factor in sporadic amyotrophic lateral sclerosis. There was no modulator effect of the SMN2 gene.