Combined genetic analyses can achieve efficient diagnostic yields for subjects with Alagille syndrome
| Project/Area Number |
17K11516
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | Nagoya City University |
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Principal Investigator |
Sugiura Tokio 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (10381881)
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| Co-Investigator(Kenkyū-buntansha) |
戸川 貴夫 名古屋市立大学, 医薬学総合研究院(医学), 助教 (10792814)
田井中 貴久 名古屋大学, 医学部附属病院, 病院講師 (30378195)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | アラジール症候群 / 胆道閉鎖症 / 次世代シーケンサー / マイクロアレイCGH / MLPA解析 / マイクロアレイCGH解析 / 次世代シークエンサー / 早期鑑別システム |
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| Outline of Final Research Achievements |
We evaluated combined genetic analyses with targeted next-generation sequencing
(NGS), multiplex ligation probe amplification (MLPA) of Jagged1 (JAG1) genes and
microarray comparative genomic hybridisation (CGH) in subjects with Alagille syndrome,incomplete clinical features of Alagille syndrome and biliary atresia. We analysed 30 subjects with Alagille syndrome, nine with incomplete Alagille syndrome and 17 with biliary atresia and detected pathogenic mutations in JAG1 or NOTCH2 in 24/30 subjects with Alagille syndrome and in 4/9 subjects with incomplete Alagille syndrome. No pathogenic mutations were detected in subjects with biliary atresia. The frequency of JAG1 mutations was as follows: single nucleotide variants (51.9%), small insertion or deletion (29.6%) and gross deletion (18.5%). Combined genetic analyses achieved efficient diagnostic yields for subjects with Alagille syndrome and incomplete Alagille syndrome.
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| Academic Significance and Societal Importance of the Research Achievements |
胆道閉鎖症とアラジール症候群の鑑別は難しい。胆道閉鎖症では、生後2 ヶ月以内の葛西手術が必要となる。一方、アラジール症候群では、葛西手術を施行すると予後が悪化する可能性がある。
我々はアラジール症候群の責任遺伝子であるJAG1 とNOTCH2 を含めた既知の原因遺伝子18個を搭載する遺伝子解析パネルを作成した。さらにMLPA、CGHアレイを組合せた包括的遺伝子解析により、胆道閉鎖症とアラジール症候群の早期鑑別システムを確立した。
胆道閉鎖症とアラジール症候群の早期鑑別に遺伝子解析は有用である。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Clinical, Pathologic, and Genetic Features of Neonatal Dubin-Johnson Syndrome: A Multicenter Study in Japan.2018
Author(s)
Togawa T, Tatsuki Mizuochi, Tokio Sugiura, Hironori Kusano, Ken Tanikawa, Takato Sasaki, Fumio Ichinose, Seiichi Kagimoto, Takahisa Tainaka, Hiroo Uchida, Shinji Saitoh
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Journal Title
The Journal of Pediatrics
Volume: -
Pages: 161-167
DOI
Related Report
Peer Reviewed
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