Moessner Rainald, Marshall Christian R, Sutcliffe James S, Skaug Jennifer, Pinto Dalila, Vincent John, Zwaigenbaum Lonnie, Fernandez Bridget, Roberts Wendy, Szatmari Peter, Scherer Stephen W
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, M5G 1L7, Canada.
Am J Hum Genet. 2007 Dec;81(6):1289-97. doi: 10.1086/522590. Epub 2007 Oct 16.
Mutations in SHANK3, which encodes a synaptic scaffolding protein, have been described in subjects with an autism spectrum disorder (ASD). To assess the quantitative contribution of SHANK3 to the pathogenesis of autism, we determined the frequency of DNA sequence and copy-number variants in this gene in 400 ASD-affected subjects ascertained in Canada. One de novo mutation and two gene deletions were discovered, indicating a contribution of 0.75% in this cohort. One additional SHANK3 deletion was characterized in two ASD-affected siblings from another collection, which brings the total number of published mutations in unrelated ASD-affected families to seven. The combined data provide support that haploinsufficiency of SHANK3 can cause a monogenic form of autism in sufficient frequency to warrant consideration in clinical diagnostic testing.
编码一种突触支架蛋白的SHANK3基因发生突变，在患有自闭症谱系障碍（ASD）的个体中已有报道。为评估SHANK3对自闭症发病机制的定量贡献，我们在加拿大确诊的400名ASD患者中确定了该基因的DNA序列和拷贝数变异频率。发现了一个新生突变和两个基因缺失，表明在该队列中的贡献率为0.75%。在另一个样本中，对两名受ASD影响的兄弟姐妹进行了另外一个SHANK3基因缺失的特征分析，这使得在无亲缘关系的受ASD影响家庭中已发表的突变总数达到七个。综合数据支持SHANK3单倍剂量不足能够以足够高的频率导致单基因形式的自闭症，值得在临床诊断检测中加以考虑。
