Comprehensive targeted next-generation sequencing in Japanese familial amyotrophic lateral sclerosis
Comprehensive targeted next-generation sequencing in Japanese familial amyotrophic lateral sclerosis
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DOI：
10.1016/j.neurobiolaging.2017.01.004
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发表时间：
2017-05-01
影响因子：
4.2
通讯作者：
Aoki, Masashi
中科院分区：
文献类型：
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作者：
Nishiyama, Ayumi;Niihori, Tetsuya;Aoki, Masashi
肌萎缩侧索硬化症（ALS）是一种以运动神经元丧失为特征的成年发病的神经退行性疾病。我们最近在日本的111个家族性ALS家系中发现了SOD 1和FUS突变是最常见的原因。为了揭示其余51例家族性ALS患者（45个家系）的可能遗传原因，我们对35个已知ALS/运动神经元疾病相关基因进行了有针对性的下一代测序。在6例患者中鉴定出ANG、OPTN、SETX和TARDBP的已知变体。在1例患者中发现了一种新的可能致病的ALS 2纯合子变体。此外，18例患者中有1- 3个新的变异，但意义不确定，而C9 ORF 72的六核苷酸重复扩增未被重复引物聚合酶链反应检测到。总的来说，在我们的日本队列中，SOD 1、FUS、SETX、TARDBP、ANG和OPTN变异体的频率分别为32%、11%、2%、2%、1%和1%。这些发现表明与家族性ALS相关的遗传变异在不同人群中存在相当大的差异。进一步的遗传分析和新的变异的功能研究是必要的。(C)2017爱思唯尔公司All rights reserved.
Amyotrophic lateral sclerosis (ALS) is anadult-onsetneurodegenerative disease characterizedby lossofmotor neurons. We have recently identified SOD1 and FUS mutations as the most common causes in a consecutive series of 111 familial ALS pedigrees in Japan. To reveal possible genetic causes for the remaining 51 patients with familial ALS (45 pedigrees), we performed targeted next-generation sequencing of 35 known ALS/motor neuron diseases-related genes. Known variants in ANG, OPTN, SETX, and TARDBP were identified in 6 patients. A novel likely pathogenic homozygous variant in ALS2 was identified in 1 patient. In addition, 18 patients harbored 1-3novelvariants of uncertainsignificance, whereas hexanucleotide repeat expansions inC9ORF72 were not detected using repeat-primed polymerase chain reaction. Collectively, in our Japanese cohort, the frequencies of SOD1, FUS, SETX, TARDBP, ANG, and OPTNvariantswere 32%, 11%, 2%, 2%, 1%, and 1%, respectively. These findings indicate considerable differences in the genetic variations associatedwith familial ALS across populations. Further genetic analyses and functional studies of novel variants are warranted. (C) 2017 Elsevier Inc. All rights reserved.