Exploring for the causative gene of Kenny-Caffey syndrome type 2

• Project/Area Number: 24791042
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: The University of Tokyo
• Principal Investigator: ISOJIMA Tsuyoshi 東京大学, 医学部附属病院, 助教 (00568230)
• Co-Investigator(Renkei-kenkyūsha): KITANAKA Sachiko 東京大学, 医学部附属病院, 准教授 (30431638)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 先天性奇形症候群 / ゲノムワイド解析 / カルシウム・リン代謝 / 遺伝子

Research Abstract

The major features of Kenny-Caffey syndrome (KCS) are proportionate short stature, cortical thickening and medullary stenosis of the tubular bones, eye abnormalities, and transient hypocalcemia. This syndrome is classified to two types by their inheritance patterns. The recessive type is KCS type 1,and the dominant type is type 2.
We explored for the causative gene for KCS type 2. We gathered all Japanese patients reported in the literatures, and collected 13 peripheral lymphocyte samples of all four patients and their family members, and obtained genome DNA with informed consent. We performed exome sequences of these samples,and found only one possible responsible gene, FAM111A with the newly established pipeline for detectiong de novo causative genes. Around the same time, another independent research group from Switzerland reported similar findings. These two independent studies confirmed that a recurrent de novo mutation of FAM111A causes KCS type 2.

Research Products

• [Journal Article] A recurrent de novo FAM111A mutation causes Kenny-Caffey syndrome type2 (2014)
  • Author(s): Isojima T, Doi K, Mitsui J, Oda Y, Tokuhiro E, Yasoda A, Yorifuji T, Horikawa R, Yoshimura J, Ishiura H, Morishita S, Tsuji S, Kitanaka S
  • Journal Title: J Bone Miner Res Volume: 29 Pages: 992-8
• [Journal Article] A recurrent de novo FAM111A mutation causes Kenny–Caffey syndrome type 2. (2013)
  • Author(s): Isojima T, Doi K, Mitsui J, Oda Y, Tokuhiro E, Yasoda A, Yorifuji T, Horikawa R, Yoshimura J, Ishiura H, Morishita S, Tsuji S, and Kitanaka S.
  • Journal Title: J Bone Mineral Res Volume: 29 Issue: 4 Pages: 992-998
  • DOI: 10.1002/jbmr.2091
  • Peer Reviewed / Open Access
• [Presentation] 次世代シークエンサーを用いたKenny-Caffey 症候群(KCS)2型の原因遺伝子の同定 (2013)
  • Author(s): 磯島豪, 土井晃一郎, 三井純, 小田洋一郎, 徳弘悦郎, 八十田明宏, 依藤亨, 堀川玲子, 吉村淳, 石浦浩之, 森下真一, 辻省次, 北中幸子
  • Organizer: 第47回日本小児内分泌学会学術集会
  • Place of Presentation: 東京
• [Presentation] 次世代シークエンサーを用いたKenny-Caffey 症候群(KCS)2型の原因遺伝子の同定 (2013)
  • Author(s): 磯島豪, 土井晃一郎, 三井純, 小田洋一郎, 徳弘悦郎, 八十田明宏, 依藤亨, 堀川玲子, 吉村淳, 石浦浩之, 森下真一, 辻省次, 北中幸子
  • Organizer: 第58回日本人類遺伝学会
  • Place of Presentation: 仙台
• [Presentation] 次世代シークエンサーを用いたKenny-Caffey症候群(KCS)2型の原因遺伝子の同定 (2013)
  • Author(s): 磯島豪, 土井晃一郎, 三井純, 小田洋一郎, 徳弘悦郎, 八十田明宏, 依藤亨, 堀川玲子, 吉村淳, 石浦浩之, 森下真一, 辻省次, 北中幸子
  • Organizer: 第47回日本小児内分泌学会学術集会
  • Place of Presentation: 東京
• [Presentation] 次世代シークエンサーを用いたKenny-Caffey症候群(KCS)2型の原因遺伝子の同定 (2013)
  • Author(s): 磯島豪, 土井晃一郎, 三井純, 小田洋一郎, 徳弘悦郎, 八十田明宏, 依藤亨, 堀川玲子, 吉村淳, 石浦浩之, 森下真一, 辻省次, 北中幸子
  • Organizer: 第58回日本人類遺伝学会
  • Place of Presentation: 仙台