Molecular genetic study of Gillespie syndrome

• Project/Area Number: 26670507
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Nagoya City University
• Principal Investigator: Saitoh Shinji 名古屋市立大学, 医学(系)研究科(研究院), 教授 (00281824)
• Co-Investigator(Kenkyū-buntansha): YOSHIYRA Koichiro 長崎大学, 原爆後障害医療研究所, 教授 (00304931) ; IHARA Yoshito 和歌山県立医科大学, 医学部, 教授 (70263241)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Gillespie症候群 / 小脳萎縮 / 虹彩欠損

Outline of Final Research Achievements

Gillespie syndrome (GS) is characterized by cerebellar ataxia, intellectual disability, and aniridia. We have performed whole exome sequencing in Japanese patients with GS, and identified de novo mutations in gene A. The identified mutations were clustered in the C terminal region of gene A, suggesting the presence of the iris specific isoform because mutations located at other than the C terminal region did not cause aniridia. We introduced V5 tag to the C terminal of mouse homolog of gene A, and investigated C terminal transcripts. Then, we successfully identified the iris specific transcript which would underly the pathogenesis of GS.