The importance of the SMN genes in the genetics of sporadic ALS

摘要

The human genome contains two SMN (survival motor neuron) genes: SMN1, the telomeric gene whose homozygousdeletion causes spinal muscular atrophy (SMA), and SMN2, the centromeric version whose copy number modulates thephenotype of SMA. We performed a Medline search and reviewed all of the publications that focus on SMN1 and SMN2 inamyotrophic lateral sclerosis (ALS) to analyse whether these genes also act as risk factors or phenotypic modulators in ALS.While homozygous deletion of SMN1 was not associated in ALS, abnormal SMN1 copy numbers significantly increased therisk of ALS. The role of the SMN2 gene in ALS needs further clarification. The existence of abnormal SMN1 copy numbersin ALS provides additional evidence that gene copy number variants may contribute to neurodegeneration and might opennew approaches to treatment.