Mutational analysis of disease causing gene in sudden death cases with cardiomyopathy or cardiac hypertrophy

• Project/Area Number: 15K19276
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Legal medicine
• Research Institution: Kagoshima University (2016-2017); Kitasato University (2015)
• Principal Investigator: Maeda Kazuho 鹿児島大学, 医歯学域医学系, 助教 (40724761)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 拡張型心筋症 / 肥大型心筋症 / 心臓性突然死 / 遺伝子解析 / サイファー遺伝子 / RNA結合モチーフ蛋白遺伝子 / 心筋症 / 心肥大 / BMP10 / RBM20 / LDB3 / FHL2 / LMNA

Outline of Final Research Achievements

We performed comprehensive genetic analysis of genes that would cause dilated cardiomyopathy (DCM) in sudden death with cardiomyopathies or concentric/dilatation hypertrophy. DCM-associated mutation was detected from one HCM case in LDB3 and other HCM case in RBM20. These HCM cases also had a mutation associated with HCM in other gene. In addition, a novel mutation was detected from one concentric hypertrophy case in RBM20. This mutation was located near to the mutation associated with HCM. These results suggested that multiple gene mutations associated with each cardiomyopathy would exacerbate cardiac function and RBM20 might be not only as DCM-causing gene but also as HCM-causing gene. Further investigation using more postmortem samples is need for proving this hypothesis and elucidating the molecular mechanism in the onset of cardiomyopathy.

Research Products

• [Journal Article] 心臓性突然死の遺伝子解析Ⅲ-SCN5A遺伝子の変異解析- (2015)
  • Author(s): 村上千香子, 前田一輔, 入江 渉, 大石桃子, 佐々木千寿子, 中丸尚美, 中村茂基, 栗原克由
  • Journal Title: DNA多型 Volume: 23 Pages: 177-180
  • Peer Reviewed
• [Presentation] 心筋症及び心肥大・拡張例における心臓特異的骨形成蛋白質10及びRNA binding motif protein 20遺伝子変異解析 (2017)
  • Author(s): 前田一輔，村上千香子，入江 渉，佐々木千寿子，佐藤文子， 栗原克由
  • Organizer: 第101次日本法医学会学術全国集会
• [Presentation] Mutational analysis of LDB3 in sudden death cases with cardiomyopathy or cardiac hypertrophy (2017)
  • Author(s): Kazuho Maeda, Chikako Murakami, Wataru Irie, Chizuko Sasaki, Fumiko Sato, Katsuyoshi Kurihara
  • Organizer: 10th International Symposium Advances in Legal Medicine
  • Int'l Joint Research
• [Presentation] 心筋症及び心肥大・拡張事例におけるラミンA/C遺伝子およびサイファー遺伝子の変異解析 (2016)
  • Author(s): 前田一輔, 村上千香子, 入江 渉, 佐々木千寿子, 中村茂基, 佐藤文子, 栗原克由
  • Organizer: 第66回日本法医学会学術九州地方集会
  • Place of Presentation: 筑水会館（福岡県久留米市）
  • Year and Date: 2016-10-14
• [Presentation] The case of 2 siblings that identified not only by DNA profiling (2015)
  • Author(s): Kazuho Maeda, Chikako Murakami, Wataru Irie, Chizuko Sasaki, Momoko Oishi, Naomi Nakamaru, Shigeki Nakamura, Katsuyoshi Kurihara
  • Organizer: 26th Congress of the International Society for Forensic Genetics
  • Place of Presentation: クラクフ (ポーランド)
  • Year and Date: 2015-08-31
  • Int'l Joint Research