Luquin Natasha, Yu Bing, Trent Ronald J, Morahan Julia M, Pamphlett Roger
Department of Pathology, Blackburn Building D06, The University of Sydney, NSW 2006, Australia.
Neuromuscul Disord. 2008 Jul;18(7):545-52. doi: 10.1016/j.nmd.2008.04.013. Epub 2008 May 27.
Mutations in the superoxide dismutase 1 gene (SOD1) are associated with familial ALS but the role of SOD1 in sporadic ALS (SALS) is unclear. We therefore sequenced the entire SOD1 gene in 23 patients with SALS. DNA was extracted from frozen pre-frontal cerebral cortex and from blood. The 5 exons, 4 introns and 1 kb upstream and downstream of SOD1 were sequenced. Novel genetic variants were found in 30% (7 of 23) brains and known variants in 91% (21 of 23) brains from patients with SALS. Two novel variants found in SALS patients and not controls were located in the SOD1 promoter and intron 1, with the promoter variant having potential functional implications. A previously described silent variant in exon 5 in one SALS patient appears to abolish an exonic splicing enhancer. All changes found in brain DNA were also found in blood DNA. In conclusion, sequencing the entire SOD1 gene revealed 3 variants in SALS patients that were not detected in controls. Although no unequivocal mutations were found, some of these variants have potential consequences for SALS pathogenesis.
超氧化物歧化酶1基因（SOD1）的突变与家族性肌萎缩侧索硬化症（ALS）相关，但SOD1在散发性ALS（SALS）中的作用尚不清楚。因此，我们对23例SALS患者的整个SOD1基因进行了测序。DNA从冷冻的前额叶大脑皮层和血液中提取。对SOD1的5个外显子、4个内含子以及上下游各1 kb进行了测序。在30%（23例中的7例）的SALS患者大脑中发现了新的基因变异，在91%（23例中的21例）的SALS患者大脑中发现了已知变异。在SALS患者而非对照中发现的两个新变异位于SOD1启动子和内含子1中，启动子变异具有潜在的功能影响。一名SALS患者外显子5中先前描述的沉默变异似乎消除了一个外显子剪接增强子。在大脑DNA中发现的所有变化在血液DNA中也均有发现。总之，对整个SOD1基因进行测序发现，SALS患者中有3个变异在对照中未被检测到。虽然未发现明确的突变，但其中一些变异可能对SALS的发病机制产生影响。
