家族性肌萎缩侧索硬化症中 SORT1 基因的分析。
Analysis of the SORT1 gene in familial amyotrophic lateral sclerosis.
机构信息
Centre of Excellence in Neurosciences of Université de Montréal, CHUM Research Center, Montreal, QC H2L 4M1, Canada.
出版信息
Neurobiol Aging. 2012 Aug;33(8):1845.e7-9. doi: 10.1016/j.neurobiolaging.2012.01.011. Epub 2012 Feb 22.
BACKGROUND
Substantial efforts have been deployed in the past decade to identify the genetic causes of amyotrophic lateral sclerosis (ALS), and we hypothesized here that mutations in SORT1 or aberrant SORT1 splicing reduce progranulin level and promote neurodegeneration.
METHODS
We sequenced the coding exons of SORT1 in a cohort of 112 unrelated individuals with familial ALS. We also tested for aberrant SORT1 splicing by RT-PCR using RNA samples from cell lines expressing six different ALS-associated TARDBP mutations.
RESULTS
We identified one unique missense and two unique silent mutations in our cohort. None are predicted to have functional effects. No aberrant SORT1 splicing event was observed.
CONCLUSIONS
SORT1 mutations are not a common cause of familial ALS, and the influence of TARDBP mutations on SORT1 splicing still needs to be clarified.
背景
过去十年，人们投入了大量精力来确定肌萎缩侧索硬化症（ALS）的遗传原因，我们在这里假设 SORT1 突变或异常 SORT1 剪接会降低颗粒蛋白前体的水平并促进神经退行性变。
方法
我们对 112 名无家族史 ALS 患者的 SORT1 编码外显子进行了测序。我们还使用来自表达六种不同 ALS 相关 TARDBP 突变的细胞系的 RNA 样本，通过 RT-PCR 测试异常的 SORT1 剪接。
结果
我们在队列中发现了一个独特的错义突变和两个独特的无义突变。这些突变都没有预测到具有功能影响。没有观察到异常的 SORT1 剪接事件。
结论
SORT1 突变不是家族性 ALS 的常见原因，TARDBP 突变对 SORT1 剪接的影响仍需阐明。
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