Identification of causative gene in congenital cataract with cognitive deficits

• Project/Area Number: 24791844
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Kitasato University (2013); Shinshu University (2012)
• Principal Investigator: KISHIMOTO Yoko 北里大学, 医学(系)研究科(研究院), 助教 (60523074)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 先天性白内障 / 家族性白内障 / 遺伝・先天異常学

Research Abstract

Congenital cataracts are the most important cause of severe visual impairment in infants. Identifying the genetic cause of congenital cataracts can be difficult because of genetic heterogeneity. We analyzed a family with congenital cataracts and identified MAF mutation by whole exome sequencing (WES). The family members showed other eye abnormalities. Congenital cataracts with MAF mutation exhibited phenotypically variable cataracts within the family. Review of the patients with MAF mutations supports the notion that congenital cataracts caused by MAF mutations could be accompanied by microcornea and/or iris coloboma. WES is a useful tool for detecting disease-causing mutations in patients with genetically heterogeneous conditions.

Research Products

• [Journal Article] Identification of a novel missense mutation of MAF in a Japanese family with congenital cataract by whole exome sequencing : a clinical report and review of literature (2014)
  • Author(s): Narumi Y, Nishina S, Tokimitsu M, Aoki Y, Kosaki R, Wakui K, Azuma N, Murata T, Takada F, Fukushima Y, Kosho T
  • Journal Title: Am J Med Genet A
  • Peer Reviewed
• [Journal Article] Identification of a novel missense mutation of MAF in a Japanese family with congenital cataract by whole exome sequencing: a clinical report and review of literature. (2014)
  • Author(s): Narumi Y, Nishina S, Tokimitsu M, Aoki Y, Kosaki R, Wakui K, Azuma N, Murata T, Takada F, Fukushima Y, Kosho T.
  • Journal Title: American Journal of Medical Genetics Part A Volume: 9999 Issue: 5 Pages: 1-5
  • DOI: 10.1002/ajmg.a.36433
  • Peer Reviewed
• [Journal Article] Availability of DMD mRNA transcripts analysis in a patient with dystrophinopathy having a nonsense mutation (2013)
  • Author(s): Narumi Y, Fueki N, Hayashi Y, Shiba N, Nishino I, Inaba Y, Kosho T, Fukushima Y, Nakamura A
  • Journal Title: Journal of neurology & translational neuroscience Volume: 1 Pages: 1005-1005
  • Peer Reviewed
• [Journal Article] Clinical consequences in truncating mutations in exon 34 of NOTCH2: Report of six patients with Hajdu-Cheney syndrome and a patient with serpentine fibula polycystic kidney syndrome. (2013)
  • Author(s): Narumi Y, Min B-J, Shimizu K, Kazukawa I, Sameshima K, Nakamura K, Kosho T, Rhee Y, Chung YS, OH Kim, Fukushima Y, Park WY, Nishimura G.
  • Journal Title: American Journal of Medical Genetics Volume: 161 Issue: 3 Pages: 518-526
  • DOI: 10.1002/ajmg.a.35772
  • Peer Reviewed
• [Journal Article] Exome sequencing in a family with an X-linked lethal malformation syndrome : clinical consequences of hemizygous truncating OFD1 mutations in male patients (2012)
  • Author(s): Tsurusaki Y, Kosho T, Hatasaki K, Narumi Y, Wakui K, Fukushima Y, Doi H, Saitsu H, Miyake N, Matsumoto N
  • Journal Title: Clin Genet Volume: (in press) Issue: 2 Pages: 135-144
  • DOI: 10.1111/j.1399-0004.2012.01885.x
  • Peer Reviewed
• [Presentation] 先天性白内障家系におけるMAF 遺伝子遺伝子新規変異の同定 (2013)
  • Author(s): 鳴海洋子, 仁科幸子, 時光元温, 青木洋子, 小崎里華, 涌井敬子, 村田敏規, 古庄知己, 福嶋義光
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 仙台
  • Year and Date: 2013-11-21
• [Presentation] Missense mutation of MAF in a Japanese family with congenital cataract (2013)
  • Author(s): Narumi Y, Nishina S, Tokimitsu M, Aoki Y, Kosaki R, Kosho T, Murata T, Takada F, Fukushima Y
  • Organizer: Annual Meeting American Society of Human Genetics
  • Place of Presentation: 米国 ボストン
  • Year and Date: 2013-10-23
• [Presentation] AKT シグナル伝達経路異常によるMPPH 症候群の臨床像 (2013)
  • Author(s): 鳴海洋子, 平林伸一, 古庄知己, 涌井敬子, 福嶋義光
  • Place of Presentation: 広島
  • Year and Date: 2013-04-18
• [Presentation] 先天性白内障家系におけるMAF遺伝子新規変異の同定 (2013)
  • Author(s): 鳴海洋子、仁科幸子、時光元温、青木洋子、小崎里華、涌井敬子、村田敏規、 古庄知己、高田史男、福嶋義光
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 宮城県、仙台市
• [Presentation] Missense mutation of MAF in a Japanese family with congenital cataract (2013)
  • Author(s): Yoko Narumi,Sachiko Nishina, Motoharu Tokimitsu, Yoko Aoki, Rika Kosaki, Tomoki Kosho,Toshinori Murata, Fumio Takada, Yoshimitsu Fukushima
  • Organizer: American Society of Human Genetics
  • Place of Presentation: 米国、ボストン
• [Presentation] Bardet-Biedl症候群の4例
  • Author(s): 才田謙、野田俊輔、鳴海洋子、小池健一
  • Organizer: 第116回日本小児科学会学術集会
  • Place of Presentation: 広島国際会議場
• [Presentation] DMD遺伝子にナンセンス変異を持つBMD児 -予後予測におけるRT-PCR検査の有用性-
  • Author(s): 鳴海洋子、中村昭則、笛木昇、林由起子、西野一三
  • Organizer: 第116回日本小児科学会学術集会
  • Place of Presentation: 広島国際会議場
• [Presentation] AKTシグナル伝達経路異常によるMPPH症候群の臨床像
  • Author(s): 鳴海洋子、平林伸一、古庄知己、涌井敬子、福嶋義光
  • Organizer: 第36回日本様に遺伝学会学術集会
  • Place of Presentation: エソール広島
• [Presentation] NOTCH2遺伝子エキソン34変異陽性患者の臨床像の検討
  • Author(s): 鳴海洋子、清水健司 、鮫島紀代子、數川逸郎、中村恒一、 Yumie Rhee、Yoon-Sok Chung、Ok-Hwa Kim、古庄知己、福嶋義光、 Woong-Yang Park、西村 玄
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 京王プラザホテル
• [Presentation] DMD遺伝子にナンセンス変異を持つBMD児 -予後予測におけるRT-PCR検査の有用性-
  • Author(s): 鳴海洋子、中村昭則、笛木昇、林由起子、西野一三
  • Organizer: 第16回小児神経学会甲信越地方会
  • Place of Presentation: 八ヶ岳ロイヤルホテル