Development of screening method for neonatal hereditary protein C deficiency and application to thrombotic disease
| Project/Area Number |
18K07849
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
藤吉 順子 九州大学, 大学病院, 助教 (20467921)
井上 普介 九州大学, 大学病院, 助教 (90467902)
落合 正行 九州大学, 医学研究院, 准教授 (90507782)
|
|---|
| Project Period (FY) |
2018-04-01 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 新生児血栓症 / プロテインC / プロテインC欠乏症 / 遺伝性プロテインC欠乏症 / 新生児 / 血栓症 |
|---|
| Outline of Final Research Achievements |
Most neonatal hereditary thrombosis is protein C deficiency. However, it is difficult to diagnose from the activity value in the neonatal period. In this study, we accumulated the clinical features and activity levels of 41 neonatal-onset protein C deficiencies with genetic testing (19 biallelic mutations, 9 monoallelic mutations, and 13 no mutations) . Moreover, a prediction formula for gene mutation detection was developed using the protein C activity value and the protein C/protein S activity ratio.
In addition, a nationwide survey of neonatal thrombosis was conducted. Five of 9 patients with protein C gene mutations had monoallelic mutations, and the genetic effects of monoallelic mutations were recognized. Seventy-five percent of the patients developed within 3 days of age (including the fetal period) regardless of the presence or absence of the mutation, suggesting the importance of early diagnosis and early treatment.
|
| Academic Significance and Societal Importance of the Research Achievements |
新生児期の血栓症は増加傾向である。小児期血栓症の20％が遺伝性であり、新生児期はプロテインC欠乏症が多い。本邦では遺伝性プロテインC欠乏症に対して活性型プロテインC製剤が保険認可されているが、新生児期は凝固・抗凝固因子活性が生理的に低く、母体・胎盤因子や周産期合併症の影響も受けるため、活性値から遺伝性を推測することは困難である。
今回過去の症例の集積より、変異検出の予測因子を明らかにし、予測式を作成した。また全国調査より、遺伝性プロテインC欠乏症の遺伝学的効果を認識し、後遺症のリスク因子となることを明らかにした。今後も早期診断および急性期治療の更なる改善が必要である。
|
Report
(6 results)
Research Products
(29 results)
-
-
[Journal Article] Stroke in a protein C-deficient infant after stem cell transplant for CHARGE syndrome.2023
Author(s)
Tanaka A, Sakaguchi Y, Inoue H, Egami N, Sonoda Y, Sonoda M, Ishimura M, Ochiai M, Hotta T, Uchiumi T, Sakai Y, Ohga S.
-
Journal Title
Pediatr Blood Cancer
Volume: 70
Issue: 4
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Ｄiagnostic challenge of the newborn patients with heritable protein C deficiency2019
Author(s)
Masako Ichiyama, Hirosuke Inoue, Masayuki Ochiai, Masataka Ishimura, Akira Shiraishi, Junko Fujiyoshi, Hironori Yamashita, Kazuo Sato, Shinya Matsumoto, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang, Toshiya Nishikubo, Akira Ishiguro, Shouichi Ohga
-
Journal Title
Ｊournal of Ｐerinatology
Volume: 39
Pages: 212-219
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
[Presentation] Diagnostic challenge of heritable protein C deficiency in the newborn infants2018
Author(s)
Masako Ichiyama, Hirosuke Inoue, Masayuki Ochiai, Masataka Ishimura, Akira Shiraishi, Junko Fujiyoshi, Hironori Yamashita, Kazuo Sato, Shinya Matsumoto, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang, Toshiya Nishikubo, Akira Ishiguro, Shouichi Ohga
Organizer
Pediatric Academic Societies Meeting
Related Report
Int'l Joint Research
-
-
