| Project/Area Number |
26860796
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Kyoto University |
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Principal Investigator |
Kawai Tomoki 京都大学, 医学(系)研究科(研究院), 助教 (20631568)
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| Co-Investigator(Renkei-kenkyūsha) |
Ohara Osamu 理化学研究所, 免疫ゲノミクス研究グループ, グループディレクター (20370926)
Suzuki Hidenori 日本医科大学, 形態解析共同研究施設, 准教授 (30158977)
Kunishima Shinji 国立病院機構名古屋医療センター, 高度診断研究部分子診断研究室, 室長 (60373495)
Oda Hirotsugu 田附興風会, 医学研究所北野病院小児科, 副部長 (20772239)
Hiejima Eitaro 京都大学, 医学部附属病院小児科, 医員 (60773520)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | FLNA / エキソンスキップ / 小児科 / 先天異常 / 小児消化器学 / 国内患者疫学調査 / 新規治療法の開発 |
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| Outline of Final Research Achievements |
Loss-of-function mutations in FLNA cause variable multiple organ complications in females and are typically lethal to males. This study investigated familial male cases with a loss-of-function mutation in FLNA who showed atypical mild clinical courses. A 4 bp deletion in exon 40 was detected, which was predicted to cause a lethalpremature protein truncation in the patietns. However, intrinsic induced in-frame skipping of the mutated exon led to the translation of a mutant FLNA missing an internal region of 41 amino acids. The exon-skipped FNLA protein was revealed to restore partially its function comparable to the wild type FLNA. The present study expands the diversity of the phenotypes associated with loss-of-function mutations in FLNA and indicated induction of exon skipping could be a theraupic option. In additon, this study indicated the usefulness of rapid daignosis using FLNA immmunnostaining of platelets.
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