Establishment of innovative method of diagnosis and prevention for functional diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H05663
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Legal medicine
• Research Institution: Hyogo Medical University (2017-2018); Nagasaki University (2015-2016)
• Principal Investigator: YAMAMOTO TAKUMA 兵庫医科大学, 医学部, 准教授 (50634458)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 機能性疾患 / 乳幼児突然死 / 法医学 / 次世代シーケンサー / RNAseq / 遺伝子変異

Outline of Final Research Achievements

Clinical exome sequencing revealed that six cases had arrhythmia-related gene variants and five cases had metabolic disease-related gene variants among 71 cases of sudden infant death. After these 11 cases were excluded, the remaining cases were defined as molecular autopsy-negative SUD and there were no significant differences in the frequency of arrhythmia-causing variants.
The case of a familial myopathy patient was analyzed. The patient had genetic variant which affected RNA splicing, and abnormal alternative splicing was detected in both cardiac and skeletal muscles. These affected isoforms might have caused the cardiac involvement with myopathy. Analyzing alternative splicing in sudden cardiac death was recommended.

Free Research Field

法医学

Academic Significance and Societal Importance of the Research Achievements

人が突然亡くなることは避けるべき問題であるにも関わらず、その原因は未だ完全に究明されているわけではない。これを解明することは本人・家族のみならず社会的にも大変有意義なことである。乳幼児や若年性の突然死の多くは遺伝子変異が原因であると考えられてきたが、徹底的に究明されるケースはそれほど多くなく今だ闇のままである。今回、clinical exome sequencing・RNAsequencingの技術を駆使し、究明にチャレンジした。結果的に、一定数の突然死症例がこれらの技術により診断できる可能性が考えられた。今後は、より簡便なより画一化した診断が広まっていくことが期待される。