Mutations in the glutaminyl-tRNA synthetase gene cause early-onset epileptic encephalopathy
Project/Area Number |
26860816
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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 | Yokohama City University |
Principal Investigator |
KODERA Hirofumi 横浜市立大学, 医学(系)研究科(研究院), 博士研究員 (70637884)
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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 |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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Keywords | てんかん性脳症 / 全エクソーム解析 / QARS / アミノアシルtRNA合成酵素 / アミノアシル化 |
Outline of Final Research Achievements |
Using whole exome sequencing, we identified compound heterozygous mutations [c.169T>C (p.Tyr57His) and c.1485dup (p.Lys496*)] in QARS, which encodes glutaminyl-tRNA synthetase, in two siblings with early-onset epileptic encephalopathy (EOEE). Recessive mutations in QARS, including the loss-of-function missense mutation p.Tyr57His, have been reported to cause intractable seizures with progressive microcephaly. The p.Lys496* mutation is novel and causes truncation of the QARS protein, leading to a deletion of part of the catalytic domain and the entire anticodon-binding domain. Transient expression of the p.Lys496* mutant in neuroblastoma 2A cells revealed diminished and aberrantly aggregated expression, indicating the loss-of-function nature of this mutant. Together with the previous report, our data suggest that abnormal aminoacylation is one of the underlying pathologies of EOEE.
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders2015
Author(s)
Ohba C, Shiina M, Tohyama J, Haginoya K, Lerman-Sagie T, Okamoto N, Blumkin L, Lev D, Mukaida S, Nozaki F, Uematsu M, Onuma A, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Tanaka F, Kato M, Ogata K, Saitsu H, Matsumoto N
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Journal Title
Epilepsia
Volume: 印刷中
Issue: 6
Pages: 841-848
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] De novo KCNT1 mutations in early-onset epileptic encephalopathy.2015
Author(s)
Ohba C, Kato M, Takahashi N, Osaka H, Shiihara T, Tohyama J, Nabatame S, Azuma J, Fujii Y, Hara M, Tsurusawa R, Inoue T, Ogata R, Watanabe Y, Togashi N, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Tanaka F, Saitsu H, Matsumoto N.
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Journal Title
Epilepsia
Volume: 56(9)
Issue: 9
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] De novo SOX11 mutations cause Coffin-Siris syndrome2014
Author(s)
Tsurusaki Y, Ohashi H, Phadke S, Koshimizu E, Kou I, Shiina M, Suzuki T, Okamoto N, Imamura S, Yamashita M, Watanabe S, Yoshiura K-i, Kodera H, Miyatake S, Nakashima N, Saitsu H, Ogata K, Ikegawa S, Miyake N, and Matsumoto N.
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Journal Title
Nat Commun
Volume: 5
Issue: 1
Pages: 4011-4011
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] PIGO mutations in intractable epilepsy and severe developmental delay with mild elevation of alkaline phosphatase levels.2014
Author(s)
Nakamura, K.Osaka, H.Murakami, Y.Anzai, R.Nishiyama, K.Kodera, H.Nakashima, M.Tsurusaki, Y.Miyake, N.Kinoshita, T.Matsumoto, N. and Saitsu, H
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Journal Title
Epilepsia
Volume: 55
Issue: 2
Pages: 13-17
DOI
Related Report
Peer Reviewed
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[Journal Article] AKT3 and PIK3R2 mutations in two patients with megalencephaly-related syndromes2014
Author(s)
Nakamura K, Kato M, Tohyama J, Shiohama T, Hayasaka K, Nishiyama K, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Matsumoto N, Saitsu H.
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Journal Title
Clin Genet
Volume: 85(4)
Issue: 4
Pages: 396-398
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] Mutations in COG2 encoding a subunit of the conserved oligomeric golgi complex cause a congenital disorder of glycosylation2014
Author(s)
Kodera H, Ando N, Yuasa I, Wada Y, Tsurusaki Y, Nakashima M, Miyake N, Saitoh S, Matsumoto N, Saitsu H.
Organizer
The American Society of Human Genetics 64th Annual Meeting
Place of Presentation
San Diego, CA, USA
Year and Date
2014-10-18 – 2014-10-22
Related Report