Functional analysis of fetal acetylcholine receptor in patients with Escobar syndrome
| Project/Area Number |
16K19639
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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 | Nagoya University |
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Principal Investigator |
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| Research Collaborator |
NATSUME jun
KIDOKORO hiroyuki
OHNO kinji
ITHO mikako
MIZUNO seiji
Engel Andrew G.
Shen Xin-Ming
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Escobar症候群 / CHRNG / 先天性筋無力症候群 / アセチルコリン受容体 / 先天性多発関節拘縮症 / 非致死型翼状片症候群 / 胎児型アセチルコリン受容体 / 脳神経疾患 / 遺伝学 / トランスレーショナルリサーチ / 脳・神経 / 神経科学 |
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| Outline of Final Research Achievements |
The nonlethal Escobar syndrome is caused by mutation in the CHRNG gene, which encodes the fetal gamma subunit of the acetylcholine receptor. We performed sequencing of CHRNG for patients with multiple joint contractures and found heterozygous mutations including one missense mutation in three patients from two families. We described clinical features and studied functional analysis using culture cells for the missense mutation. Although the clinical features of Escobar syndrome are variable but the condition is characterized by pterygia, all three patients had very mild pterygia. We conducted expression experiments and channel functional analyses using culture cells. We revealed that the mutation cause the fetal fast channel syndrome with abnormally brief opening and activity of the channel.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで成人型の骨格筋アセチルコリン受容体のチャネル動態異常による疾患は先天性筋無力症候群の一型として報告されているが、胎児型アセチルコリン受容体での報告はなかった。今回Escobar症候群3症例で同定した共通の遺伝子変異について胎児型アセチルコリン受容体の機能解析をおこない、発現量の低下とチャネル開口時間の異常によることを明らかにした。3症例は臨床像が類似しており、Escobar症候群で特徴的とされている翼状片が非常に軽微だった。先天性多発関節拘縮症には多数の原因があるが、翼状片が軽微であってもCHRNG変異を考える必要がある。
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Report
(4 results)
Research Products
(3 results)
