| Project/Area Number |
15K08619
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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 |
Laboratory medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
Okumiya Toshika 熊本大学, 大学院生命科学研究部(保), 教授 (50284435)
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| Research Collaborator |
NAKAMURA KIMITOSHI 熊本大学, 大学院生命科学研究部, 教授 (30336234)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ポンペ病 / 酸性α－グルコシダーゼ / 新生児マススクリーニング / Ⅱ型糖原病 / ライソゾーム病 / 乾燥血液濾紙 / Ⅱ糖原病 / 酸性マルターゼ / 血液濾紙 / 遺伝子多型 / 新生児スクリーニング / common mutation / スプライス異常 / リソソーム病 |
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| Outline of Final Research Achievements |
We have performed newborn screening for Pompe disease with dried blood spots in Japanese population, from April 2013 to November 2016, in which 103,204 newborns were screened. 71 had low acid alpha-glucosidase (AαGlu) activity. GAA sequencing showed that 32(45.1%) homozygotes and 37 (52.1%) heterozygotes for pseudodeficiency alleles [1726G>A; 2965G>A], respectively. Eight of 32 newborns with homozygous [1726G>A; 2965G>A] alleles had one mutation each. Two of 37 newborns with heterozygous [1726G>A; 2965G>A] alleles had two mutations each. Only one newborn who had two mutations did not harbor [1726G>A; 2965G>A] alleles. Based on these data, no infantile-onset Pompe disease was detected, and three newborns were diagnosed with potential late-onset Pompe disease. It was difficult to distinguish newborns with [1726G>A; 2965G>A] alleles from newborns with pre-symptomatic Pompe disease using AαGlu assays in DBSs or fibroblasts, GAA gene sequencing was necessary.
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| Academic Significance and Societal Importance of the Research Achievements |
申請者は日本人新生児103,204例を対象に、アジア人固有の多型[c.1726G>A;c.2065G>A]の迅速解析法と当該遺伝子多型の影響を低減したBa/Zn法、ならびに次世代シークエンサーによる遺伝子解析を技術基盤として、わが国初のポンペ病マスクスリーニングを実施した。その結果、血液濾紙(Ba/Zn法含む)や培養線維芽細胞による活性測定だけでは、最終診断まで至らないことが示され、次世代シークエンサーを用いたAαGlu遺伝子解析が有効であることが示唆された。この早期診断により、より速い治療介入が可能となり、患者のQOLやADLを顕著に完全できるものと思われた。
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