Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Neurobiol Aging. 2012 Aug;33(8):1843.e19-24. doi: 10.1016/j.neurobiolaging.2011.12.037. Epub 2012 Mar 7.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective motor neuron death in the brain and spinal cord. Many disease genes for ALS have been identified; however, each disease gene is responsible for very small fractions of ALS. Recently, mutations of the gene encoding optineurin (OPTN) are reported in familial and sporadic ALS. OPTN is also responsible for a small number of ALS, 3.8% of familial and 0.29% of sporadic ALS in Japanese. The low prevalence may be an underestimation due to incomplete screening of the mutation. To examine OPTN mutations more extensively, we screened the OPTN deletions using a quantitative PCR system. We examined 710 Japanese ALS subjects who had previously been found to have no OPTN mutations by a screening using a PCR-direct sequence strategy. We identified 3 kinds of deletions in 5 patients; one was homozygous, and the remaining were heterozygous. All deletions occurred due to the Alu-mediated recombination and are expected to result in null alleles. Our results suggest that the OPTN deletion mutation in ALS is not infrequent and the prevalence of the OPTN mutation in Japanese sporadic ALS is considerably high.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是大脑和脊髓中的选择性运动神经元死亡。已经确定了许多 ALS 的疾病基因；然而，每个疾病基因仅负责 ALS 的很小一部分。最近，在家族性和散发性 ALS 中报道了编码视神经萎缩蛋白（OPTN）的基因突变。OPTN 也是少数 ALS 的原因，在日本，家族性 ALS 占 3.8%，散发性 ALS 占 0.29%。由于突变筛查不完全，低患病率可能是低估了。为了更广泛地检查 OPTN 突变，我们使用定量 PCR 系统筛选 OPTN 缺失。我们检查了 710 名日本 ALS 患者，他们之前通过使用 PCR 直接测序策略进行筛查未发现 OPTN 突变。我们在 5 名患者中发现了 3 种缺失；一种是纯合子，其余为杂合子。所有缺失都是由于 Alu 介导的重组而发生的，预计会导致无效等位基因。我们的结果表明，ALS 中的 OPTN 缺失突变并不罕见，日本散发性 ALS 中 OPTN 突变的患病率相当高。
