Corcia Philippe, Camu William, Praline Julien, Gordon Paul H, Vourch Patrick, Andres Christian
ALS Centre, CHU Tours, INSERM, Université François-Rabelais, 2 Boulevard Tonnellé, Tours Cedex 1, France.
Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):436-40. doi: 10.3109/17482960902759162.
The human genome contains two SMN (survival motor neuron) genes: SMN1, the telomeric gene whose homozygous deletion causes spinal muscular atrophy (SMA), and SMN2, the centromeric version whose copy number modulates the phenotype of SMA. We performed a Medline search and reviewed all of the publications that focus on SMN1 and SMN2 in amyotrophic 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 the risk of ALS. The role of the SMN2 gene in ALS needs further clarification. The existence of abnormal SMN1 copy numbers in ALS provides additional evidence that gene copy number variants may contribute to neurodegeneration and might open new approaches to treatment.
人类基因组包含两个SMN（生存运动神经元）基因：SMN1，即端粒基因，其纯合缺失会导致脊髓性肌萎缩症（SMA）；以及SMN2，着丝粒版本的基因，其拷贝数可调节SMA的表型。我们进行了医学文献数据库检索，并回顾了所有聚焦于肌萎缩侧索硬化症（ALS）中SMN1和SMN2的出版物，以分析这些基因在ALS中是否也作为风险因素或表型调节因子发挥作用。虽然SMN1的纯合缺失与ALS无关，但异常的SMN1拷贝数显著增加了患ALS的风险。SMN2基因在ALS中的作用需要进一步阐明。ALS中存在异常的SMN1拷贝数提供了额外证据，表明基因拷贝数变异可能导致神经退行性变，并可能开辟新的治疗途径。
