Comprehensive whole genome sequence analysis using a long read sequencer for delineating molecular mechanism of neurological diseases

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H05085
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: The University of Tokyo
• Principal Investigator: Ishiura Hiroyuki 東京大学, 医学部附属病院, 助教 (40632849)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: リピート伸長変異

Outline of Final Research Achievements

In benign adult familial myoclonic epilepsy (BAFME), expansions of intronic TTTCA and TTTTA repeats were identified in SAMD12, TNRC6A, and RAPGEF2. A new concept of repeat motif-phenotype correlation was proposed. The finding strongly indicates the gain-of-function of the expanded repeats is pathomechanism of BAFME.
The study also indicate the importance of genetic analysis focusing on repeat expansions. By applying this strategy to neuronal intranuclear inclusion disease, oculopharyngeal myopathy with leukoencephalopathy, and oculopharyngodistal myopathy, CGG repeat expansions were identified in NOTCH2NLC, LOC642361/NUTM2B-AS1, LRP12, respectively.

Free Research Field

神経遺伝学

Academic Significance and Societal Importance of the Research Achievements

良性成人型家族性ミオクローヌスてんかんの原因が、タンパク質に翻訳されない部分に存在するリピート伸長変異であることを発見した。また、3つの別個の遺伝子に存在するリピート伸長変異が同様の疾患を引き起こすという、てんかんにおける新しい機序を発見した。
同様の手法を応用し、神経核内封入体病、白質脳症を伴う眼咽頭型ミオパチー、眼咽頭遠位型ミオパチーについてもリピート伸長変異を新たに同定することに成功した。