Elucidation of developmental mechanisms of the bilateral vestibular schwannoma in neurofibromatosis type 2 using patient-derived iPS cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20276
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Keio University
• Principal Investigator: Matsuzaki Saeko 慶應義塾大学, 医学部(信濃町), 共同研究員 (70573400)
• Research Collaborator: OISHI Naoki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 神経線維腫症２型 / 聴神経腫瘍 / 遺伝性難聴 / NF２ / iPS細胞 / ヒトiPS細胞

Outline of Final Research Achievements

In the research of hereditary diseases with hiPS cells, repairing gene mutations is in general an indispensable step for confirming phenotypes at the cellular level. Therefore, in this study, we first identified mutations in the NF2 gene before establishing hiPS cells. DNA was extracted from the peripheral blood of 7 patients (3 males and 4 females) who had bilateral acoustic nerve tumors defined by MRI and were clinically diagnosed as NF2. Gene analysis was performed with a next-generation sequencer. Pathogenic variants were found in NF2 gene in 5 cases, likely pathogenic variant in 1 case. We are currently working on establishing patient-derived iPS cells from pathogenic mutant cases with severe symptoms.

Free Research Field

遺伝性難聴

Academic Significance and Societal Importance of the Research Achievements

神経線維腫症2型の患者由来iPS細胞を樹立するにあたり、まずは末梢血を用いてNF2患者の遺伝子変異の解析を行った。遺伝子変異と実際の臨床像を検討中であり、今回の研究成果により病原性の高い遺伝子変異症例を選択しiPS細胞を樹立することが可能となる。よってより効率的に神経線維腫症2型の病態を解明できると考えられる。