Indentification of causative genes of cavernous angiomas by whole exome sequencing and targeted sequencing

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16574
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Kengo Hirota 東京女子医科大学, 医学部, 助教 (10532690)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 海綿状血管腫 / 次世代シーケンサー / 遺伝子

Outline of Final Research Achievements

Familial cerebral cavernous malformation (CCM) of this condition are autosomal-dominantly inherited via CCM1, CCM2, and CCM3 mutations. We performed targeted resequencing of CCM1,2,3 using next-generation sequencer in 5 cases of familial CCM, 3 cases of multiple CCM. As a result, CCM2 mutations was identified in 2 cases of familial CCM, and CCM1 mutations was identified in 2 cases of multiple CCM. One of the CCM2 mutations was a novel nonsense mutation that had never been reported. In the case of multiple CCM, it may be possible that genetic factors are potentially involved. Therefore, it is important to genetic screening in the case of multiple CCM. In addition, genetic analysis using a next-generation sequencer targets point mutations and small indels, improving the analysis method are needed to identify for other causes such as large deletion and copy number variant.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

海綿状血管腫の治療方法については、症候性であれば外科的な治療法しか方策がなく、出血前診断や予防治療などはない。これまで本邦での海綿状血管腫の遺伝解析の報告は、少数である。今回の研究で本邦での遺伝解析のデータを蓄積しただけでなく、多発性海綿状血管腫においても、遺伝子変異が同定されていることから潜在的に遺伝要因がある海綿状血管腫の症例は多いのではないかと考える。海外において創薬研究も進んでおり、本邦での海綿状血管腫の遺伝解析データの蓄積は、今後の新たな治療法の確立するうえで必要な基礎データであり今後も研究の継続が必要であると考えられる。