Genetic analysis of adult leukoencephalopathy patients using a custom-designed gene panel
Genetic analysis of adult leukoencephalopathy patients using a custom-designed gene panel
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DOI：
10.1111/cge.13371
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发表时间：
2018-08-01
影响因子：
3.5
通讯作者：
Tanaka, F.
中科院分区：
文献类型：
--
作者：
Kunii, M.;Doi, H.;Tanaka, F.
脑白质病包括所有主要影响脑白质的临床综合征。遗传诊断为这些患者的临床管理提供了依据，但成人白质脑病的大部分遗传因素仍未得到解决。为了检验这种遗传贡献，我们使用定制设计的基因面板，通过下一代测序分析了60名日本不明原因成人白质脑病患者的基因组DNA。我们选择了55个白质脑病相关基因作为基因面板。我们在60例成人白质脑病患者中鉴定了8例（13.3%）的致病突变：5例患者检测到NOTCH3突变，EIF2B2、CSF1R和POLR3A分别在1例患者中独立发现突变。这些结果表明，NOTCH3突变引起的大脑常染色体显性动脉病变伴皮质下梗死和脑白质病（CADASIL）是我们队列中最常见的成人脑白质病。此外，脑成像分析表明，如果不进行遗传检查，没有表现出典型表型的CADASIL患者可能会被误诊。
Leukoencephalopathies encompass all clinical syndromes that predominantly affect brain white matter. Genetic diagnosis informs clinical management of these patients, but a large part of the genetic contribution to adult leukoencephalopathy remains unresolved. To examine this genetic contribution, we analyzed genomic DNA from 60 Japanese patients with adult leukoencephalopathy of unknown cause by next generation sequencing using a custom-designed gene panel. We selected 55 leukoencephalopathy-related genes for the gene panel. We identified pathogenic mutations in 8 of the 60 adult leukoencephalopathy patients (13.3%): NOTCH3 mutations were detected in 5 patients, and EIF2B2, CSF1R, and POLR3A mutations were found independently in 1 patient each. These results indicate that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations is the most frequent adult leukoencephalopathy in our cohort. Moreover, brain imaging analysis indicates that CADASIL patients who do not present typical phenotypes may be underdiagnosed if not examined genetically.