Investigation of pathology and development of specific medial care system and treatment associated with FLNA deficiency
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 |
Research Field |
Pediatrics
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Research Institution | Kyoto University |
Principal Investigator |
Kawai Tomoki 京都大学, 医学(系)研究科(研究院), 助教 (20631568)
|
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)
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
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 |
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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Report
(3 results)
Research Products
(2 results)
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[Journal Article] Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function2016
Author(s)
Oda H., Sato T., Kunishima S., Nakagawa K., Izawa K., Hiejima E., Kawai T., Yasui T., Doi H., Katamura K., Numabe H., Okamoto S., Nakase H., Hijikata A., Ohara O., Suzuki H., Morisaki H., Morisaki T., Nunoi H., Hattori S., Nishikomori R., Heike T.
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Journal Title
Eur J Hum Genet
Volume: 24
Issue: 3
Pages: 408-414
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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