2022 Fiscal Year Final Research Report
Development of screening method for neonatal hereditary protein C deficiency and application to thrombotic disease
| Project/Area Number |
18K07849
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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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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Keywords | 新生児血栓症 / プロテインC |
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| 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.
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| Free Research Field |
新生児
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| 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。
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