Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Neurobiol Aging. 2012 Apr;33(4):786-90. doi: 10.1016/j.neurobiolaging.2010.06.017. Epub 2010 Aug 2.
Mutations in TARDBP encoding TDP (TAR DNA binding protein)-43 have been reported in familial and sporadic amyotrophic lateral sclerosis (ALS), but mostly in Caucasians. In other ethnic groups, four types of mutations are found in familial ALS. In sporadic ALS, the TARDBP mutations frequency is low in Caucasians (0-5%) and no mutation has been found in other ethnic groups. To examine spectrum of TARDBP mutations and its frequency in Japanese, we screened the TARDBP mutation in 721 Japanese ALS by direct sequencing. We identified a novel mutation, c.1069G > A (p.Gly357Ser) and a known mutation in sporadic ALS. One patient was homozygous for p.Gly357Ser, which was the first for TARDBP mutation. Our study showed that TARDBP mutations also occur in non-Caucasian sporadic ALS. The estimated frequency of the TARDBP mutation in sporadic ALS is 0.29% in Japanese. The mutation frequency in familial ALS in Japanese is also similar to that in Caucasian, and is ∼10 times higher than that in Japanese sporadic ALS.
TDP（TAR DNA 结合蛋白）-43 编码 TARDBP 的突变已在家族性和散发性肌萎缩侧索硬化症（ALS）中报道，但主要在白种人中。在其他种族群体中，家族性 ALS 中发现了四种类型的突变。在散发性 ALS 中，白种人中 TARDBP 突变的频率较低（0-5%），而在其他种族中未发现突变。为了研究 TARDBP 突变谱及其在日本人中的频率，我们通过直接测序筛选了 721 例日本 ALS 中的 TARDBP 突变。我们鉴定出一种新的突变 c.1069G > A（p.Gly357Ser）和一种散发性 ALS 中的已知突变。一名患者为 p.Gly357Ser 纯合子，这是 TARDBP 突变的首例。我们的研究表明，TARDBP 突变也发生在非白种人散发性 ALS 中。在日本，散发性 ALS 中 TARDBP 突变的估计频率为 0.29%。日本家族性 ALS 中的突变频率与白种人相似，是日本散发性 ALS 的约 10 倍。
