Genetic mechanism of split-hand/foot malformation with or without long bone deficiency

• Project/Area Number: 26870255
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human genetics; Pediatrics
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Nagata Eiko 浜松医科大学, 医学部附属病院, 特任助教 (90535569)
• Co-Investigator(Renkei-kenkyūsha): Fukami Maki 国立成育医療研究センター, 分子内分泌研究部, 部長 (40265872) ; Ogata Tsutomu 浜松医科大学, 小児科, 教授 (40169173)
• Project Period (FY): 2014-02-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 先天異常 / 遺伝子解析 / 臨床遺伝学 / 裂手裂足症 / 原因遺伝子 / 人類遺伝学 / 小児科学 / 先天奇形 / 整形外科学

Outline of Final Research Achievements

BHLHA9 copy-number gain constitutes a strong susceptibility factor with a dosage effect for limb malformations. Japanese founder duplication was generated through a replication-based mechanism and underwent subsequent triplication and haplotype modification through recombination- based mechanisms. Clinical variability appears to be due to multiple factors.

Research Products

• [Journal Article] Femoral-tibial-digital malformations in a boy with the Japanese founder triplication of BHLHA9. (2015)
  • Author(s): Nagata E, Haga N, Fujisawa Y, Fukami M, Nishimura G, Ogata T.
  • Journal Title: Am J Med Genet A Volume: 167 Issue: 12 Pages: 3226-3228
  • DOI: 10.1002/ajmg.a.37290
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Japanese founder duplications/triplications involving BHLHA9 are associated with split-hand/foot malformation with or without long bone deficiency and Gollop-Wolfgang complex. (2014)
  • Author(s): Nagata E, Kano H, Kato F, Yamaguchi R, Nakashima S, Takayama S, Kosaki R, Tonoki H, Mizuno S, Watanabe S, Yoshiura KI, Kosho T, Hasegawa T, Kimizuka M, Suzuki A, Shimizu K, Ohashi H, Haga N, Numabe H, Horii E, Nagai T, Yoshihashi H, Nishimura G, Toda T, et al.
  • Journal Title: Orphanet J Rare Dis Volume: 9 Issue: 1 Pages: 125-125
  • DOI: 10.1186/s13023-014-0125-5
  • Peer Reviewed / Open Access
• [Presentation] 若手シンポジウム (2016)
  • Author(s): 永田絵子
  • Organizer: 日本小児遺伝学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-09
  • Invited
• [Presentation] HOXDクラスターを含む2q31領域ヘテロ欠失と外陰部・四肢形成不全 (2015)
  • Author(s): 永田絵子
  • Organizer: 第49回日本小児内分泌学会学術集会
  • Place of Presentation: タワーホール船堀
  • Year and Date: 2015-10-08
• [Presentation] BHLHA9を含む約200 kbの同一領域の日本人創始者コピー数増加は四肢形成不全発症の顕著な感受性因子である (2014)
  • Author(s): 永田絵子
  • Organizer: 日本小児内分泌学会
  • Place of Presentation: アクトシティ浜松
  • Year and Date: 2014-09-25 – 2014-09-27