Establishment of diagnosis method and analysis of genetic background of adult leukoencephalopathy patients with desktop next-generation sequencer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461287
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Yokohama City University
• Principal Investigator: Ueda Naohisa 横浜市立大学, 大学病院, 准教授 (00305442)
• Co-Investigator(Kenkyū-buntansha): DOI Hiroshi 横浜市立大学, 医学部神経内科, 准教授 (10326035) ; TANAKA Fumiaki 横浜市立大学, 医学研究科神経内科, 教授 (30378012)
• Co-Investigator(Renkei-kenkyūsha): MATSUMOTO Naomichi 横浜市立大学, 医学研究科遺伝学, 教授 (80325638)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 次世代シーケンサー / カスタムキャプチャー / 白質脳症

Outline of Final Research Achievements

Leukoencephalopathies comprise all clinical syndromes predominantly affecting the white matter of the brain. We performed capture-based target enrichment followed by next-generation sequencing for the genetic screening of adult leukoencephalopathy patients with unknown causes. We picked up 55 leukoencephalopathy-related genes and designed the bait library with SureSelect technology (Agilent). Genomic DNAs from 60 Japanese adult leukoencephalopathy patients were processed by this library, and the captured DNAs were analyzed by next generation sequencer MiSeq. As results, we detected pathological NOTCH3 mutations in 4 patients, and EIF2B2 and POLR3A mutations in one patient, respectively. Additionally, unreported mutations were detected in some patients. In our study, 10% of adult patients with leukoencephalopathy were definitively diagnosed with known or apparently pathological mutations, and 8.3% of patients had mutations with unconfirmed significance.

Free Research Field

神経変性疾患