Research on genetic pathomechanism of adult-onset white matter disease

• Project/Area Number: 16K09698
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Yoshida Tomokatsu 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (90457987)
• Co-Investigator(Kenkyū-buntansha): 水野 敏樹 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30264782) ; 水田 依久子 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80397760)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 脳白質疾患 / エキソーム解析 / 遺伝性疾患 / 小血管病 / 脳神経疾患 / 遺伝子 / 遺伝学

Outline of Final Research Achievements

LAMB1 gene encodes laminin subunit beta 1, a constituent of the extracellular matrix glycoprotein of basement membranes. Mutations of LAMB1 gene have been reported in patients with congenital or infantile- to childhood-onset leukoencephalopathy and severe developmental retardation. We report the first adulthood-onset case with mild leukoencephalopathy and a novel homozygous LAMB1gene missense mutation. Our findings expand the clinical spectrum of LAMB1-related disorder.

Academic Significance and Societal Importance of the Research Achievements

次世代シークエンサー（エキソーム解析）による遺伝子解析を行い、基底膜の構成成分であるLAMB1遺伝子変異が成人発症白質脳症の原因である可能性を報告した。LAMB1関連疾患の幅広い臨床像が明らかになることで、これまで原因不明とされてきた成人発症白質脳症の診断に寄与することが期待される。LAMB1関連疾患の症例が蓄積されることで、病態解明と疾患特異的治療法の開発につながることが望まれる。

Research Products

• [Journal Article] Adult-onset leukoencephalopathy with homozygous LAMB1 missense mutation (2020)
  • Author(s): Yasuda R, Yoshida T, Mizuta I, Watanabe M, Nakano M, Sato R, Tokuda Y, Omi N, Sakai N, Nakagawa M, Tashiro K, Mizuno T.
  • Journal Title: Neurology Genetics Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] アレキサンダー病の臨床と病態 (2017)
  • Author(s): 吉田誠克
  • Journal Title: Dementia Japan Volume: 31 Pages: 10-17
  • NAID: 40021803630
• [Presentation] Adult-onset leukoencephalopathy with homozygous LAMB1 missense mutation (2020)
  • Author(s): 安田 怜
  • Organizer: 第61回日本神経学会学術大会
• [Presentation] Genetic causes of cerebral small vessel disease. (2018)
  • Author(s): Mizuno T.
  • Organizer: 16th Asian Oceanian Congress of Neurology．
  • Int'l Joint Research
• [Presentation] Potential Mechanisms of stroke in CADASIL. (2018)
  • Author(s): Mizuno T.
  • Organizer: The 9th International Conference of The International Society of Vascular Behavioural and Cognitive Disorders.
  • Int'l Joint Research
• [Presentation] 晩期発症型アレキサンダー病の発症年齢に関連する遺伝的変異の検討. (2018)
  • Author(s): 安田怜，吉田誠克，中野正和，佐藤隆一，足立博子，徳田雄市，水田依久子，齋藤光象，松浦 潤，中川正法，田代啓，水野敏樹．
  • Organizer: 第59回日本神経学会学術大会．