Genetic analysis of a new syndrome with aberrant JAK2 splicing

• Project/Area Number: 23591550
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyorin University
• Principal Investigator: OHNISHI Hiroaki 杏林大学, 医学部, 准教授 (80291326)
• Co-Investigator(Kenkyū-buntansha): WATANABE Takashi 杏林大学, 医学部, 教授 (00191768) ; OHTSUKA Kouki 杏林大学, 医学部, 助教 (70439165)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: JAK2 / スプライシング異常 / 骨髄増殖性腫瘍 / GATA1 / スプライシング / 先天性骨髄増殖性腫瘍 / DGKK / ＪＡＫ２ / 先天異常

Outline of Final Research Achievements

We found a JAK2 splicing mutation in an infant and a fetus presenting with myeloproliferative neoplasm and genital anomalies. No enhancement of phosphorylation of downstream signal molecules was observed in cell lines with this JAK2 mutation. Transgenic mice with this aberrant JAK2 did not develop hematopoietic abnormalities or genital anomalies. To explore the underlying mechanism causing these clinical features and aberrant JAK2 splicing, we performed exome analysis for these patients and their parents and siblings. We identified G221D mutation of GATA1 gene located on X chromosome in these patients and their mother, suggesting that GATA1 mutation is associated with the hematopoietic abnormalities in these patients. In addition, we found mutations in DGKK gene, which is reported to be related to hypospadias, suggesting that DGKK mutation is associated with the genital anomalies in these patients.

Research Products

• [Presentation] 遺伝性骨髄増殖性腫瘍の家族例における網羅的遺伝子解析 (2014)
  • Author(s): 大西 宏明, 滝田 順子, 松島 早月, 大塚 弘毅, 岸野 智則, 細井 健一郎, 大倉 康夫, 小川 誠司, 渡邊 卓
  • Organizer: 日本臨床検査医学会
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-22 – 2014-11-25
• [Presentation] JAK2 SPLICING MUTATION IN SIBLINGS PRESENTING WITH MYELOPROLIFERATIVE NEOPLASMS, CARDIOMYOPATHY AND HYPOGONADISM (2011)
  • Author(s): Hiroaki Ohnishi, Ken-ichirou Hosoi, Hiroshi Yoshino, Yuki Gemma, Kouki Ohtsuka, Satsuki Matsushima, Fumio Bessho, Takashi Watanabe, Fujino Takashi
  • Organizer: 43th Congress of the International Society of Paediatric Oncology
  • Place of Presentation: Auckland, New Zealand