Comprehensive analysis and identification of novel genes in adult leukoencephalopathy by short and long read sequencing.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16581
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Yokohama City University
• Principal Investigator: MIYAKE Ryoko 横浜市立大学, 医学研究科, 客員研究員 (10760184)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: leukoencephalopathy / genetics

Outline of Final Research Achievements

The disease background of leukoencephalopathy is very diverse, and an accurate diagnosis is essential to consider its appropriate treatment of the disease. However, it is not easy to make a precise diagnosis based on clinical and imaging findings.In this study, we aimed to clarify the genetic background of adult leukoencephalopathy by reanalyzing 81 cases in which the diagnosis was not confirmed in our previous studies and by performing genetic analysis of 50 newly collected cases. In the reanalysis of the previously undetermined cases, copy number analysis, long read sequence analysis, and RNA sequence analysis allowed us to identify the genetic cause in two cases. Further analysis of newly colleted 50 cases identified a genetic cause in 14 cases, 5 of which had neuronal nuclear inclusion body disease and 6 of which had CADASIL.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

我々の先行研究、本研究を通じて、成人白質脳症患者160症例の遺伝学的解析を行い、17例がNIID、17例がCADASILであった。その他は稀少疾患でありCSF1R、EIF2B2、POLR3A、L2HGDH、TUBB4A、YWHAE、DARS2、HTRA1、RRM2B、COL4A1解析のバリアントが原因である症例が1例ずつで、原因が判明したのは44例/160例（27.5％）であった。
本研究により成人白質脳症の遺伝学的背景の一端が明らかとなり、成人白質脳症の診断、治療に有益なデータを提供できたと考えられる。