Identification and functional analysis of a new candidate gene of nemaline myopathy
Project/Area Number |
25860876
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
|
Research Institution | Yokohama City University |
Principal Investigator |
IMAMURA Eriko 横浜市立大学, 医学(系)研究科(研究院), 博士研究員 (80637877)
|
Project Period (FY) |
2013-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
Keywords | 先天性ミオパチー / エクソーム解析 / ゼブラフィッシュ / エキソーム解析 |
Outline of Final Research Achievements |
By whole exome sequencing, compound heterozygous mutation was identified in new candidate gene KLHL40 from a Japanese family with nemaline myopathy (NEM). A multinational cohort of 143 severe NEM patients lacking genetic diagnosis revealed that 19 mutations in KLHL40 in 28 NEM family. Molecular modeling suggested that the missense mutations would destabilize the protein. Protein studies showed that KLHL40 is a skeletal muscle specific protein that is absent in patient skeletal muscle. In zebrafish, knockdown of klhl40 resulted in disruption of muscle structure. These results indicated that the mutations of KLHL40 gene caused NEM.
|
Report
(3 results)
Research Products
(15 results)
-
[Journal Article] Detecting copy-number variations in whole-exome sequencing data using the eXome Hidden Markov Model: an 'exome-first' approach.2015
Author(s)
Miyatake S, Koshimizu E, Fujita A, Fukai R, Imagawa E, Ohba C, Kuki I, Nukui M, Araki A, Makita Y, Ogata T, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Matsumoto N
-
Journal Title
Journal of Human Genetics
Volume: 60
Pages: 175-182
Related Report
Peer Reviewed
-
[Journal Article] De novo SOX11 mutations cause Coffin-Siris syndrome.2014
Author(s)
Tsurusaki Y, Koshimizu E, Ohashi H, Phadke S, Kou I, Shiina M, Suzuki T, Okamoto N, Imamura S, Yamashita M, Watanabe S, Yoshiura K, Kodera H, Miyatake S, Nakashima M, Saitsu H, Ogata K, Ikegawa S, Miyake N, Matsumoto N
-
Journal Title
Nature Communications
Volume: 5
Pages: 4011-4011
Related Report
Peer Reviewed
-
[Journal Article] Deep sequencing detects very-low-grade somatic mosaicism in the unaffected mother of siblings with nemaline myopathy2014
Author(s)
Miyatake S, Koshimizu E, Hayashi YK, Miya K, Shiina M, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Ogata K, Nishino I, Matsumoto N
-
Journal Title
Neuromuscular Disorders
Volume: 24
Pages: 642-647
Related Report
Peer Reviewed / Acknowledgement Compliant
-
[Journal Article] Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy2013
Author(s)
Ravenscroft G, Miyatake S, Hayashi YK, Miyake N, Tsurusaki Y, Doi H, Saitsu H, Osaka H, Yamashita S, Ohya T, Sakamoto Y, Koshimizu E, Imamura S, Yamashita M, Ogata K, Shiina M, Bryson-Richardson RJ, Nishino I, Matsumoto N, Laing NG, et al
-
Journal Title
Am J Hum Genet
Volume: 93
Pages: 6-18
Related Report
Peer Reviewed
-
-
[Journal Article] De Novo mutations in GNAO1, encoding a Gαo subunit of heterotrimeric G proteins, cause epileptic encephalopathy2013
Author(s)
Nakamura K, Kodera H, Akita T, Shiina M, Kato M, Hoshino H, Terashima H, Osaka H, Nakamura S, Miyatake S, Koshimizu E, Nishiyama K, Nakashima M, Tsurusaki Y, Miyake N, Hayasaka K, Ogata K, Fukuda A, Matsumoto N, Saitsu H, et al
-
Journal Title
Am J Hum Genet
Volume: 93
Pages: 496-505
Related Report
Peer Reviewed
-
[Journal Article] MLL2 and KDM6A mutations in patients with Kabuki syndrome2013
Author(s)
Miyake N, Koshimizu E, Okamoto N, Mizuno S, Ogata T, Nagai T, Kosho T, Ohashi H, Kato M, Sasaki G, Kitanaka S, Matsubara Y, Makita T, Taguri M, Nakashima M, Tsurusaki Y, Saitsu H, Yoshiura K, Matsumoto N, Niikawa N, et al
-
Journal Title
Am J Med Genet A
Volume: 161
Pages: 2234-2243
Related Report
Peer Reviewed
-
[Journal Article] Whole-exome sequencing identified a homozygous FNBP4 mutation in a family with a condition similar to microphthalmia with limb anomalies2013
Author(s)
Kondo Y, Koshimizu E, Megarbane A, Hamanoue H, Okada I, Nishiyama K, Kodera H, Miyatake S, Tsurusaki Y, Nakashima M, Doi H, Miyake N, Saitsu H, Matsumoto N.
-
Journal Title
Am J Med Genet A
Volume: 161
Pages: 1543-1546
Related Report
Peer Reviewed
-
[Presentation] 次世代シーケンサーを用いた超低頻度モザイク変異の検出:ネマリンミオパチーの一例.2014
Author(s)
輿水江里子, 宮武聡子, 林由起子, 宮一志, 椎名政昭, 中島光子, 鶴崎美徳, 三宅紀子, 才津浩智, 緒方一博, 西野一三, 松本直通
Organizer
日本人類遺伝学会第59回大会
Place of Presentation
タワーホール船堀(東京)
Year and Date
2014-11-19 – 2014-11-22
Related Report
-
[Presentation] Deep sequencing detects very low-grade somatic mosaicism in the unaffected mother of siblings with nemaline myopathy.2014
Author(s)
Koshimizu E, Miyatake S, Hayashi K Y, Miya K, Shiina M, Nakashima, M, Tsurusaki Y, Miyake N, Saitsu H, Ogata K, Nishino I, Matsumoto N
Organizer
American Society of Human Genetics 64th Annual Meeting
Place of Presentation
San Diego, USA
Year and Date
2014-10-18 – 2014-10-22
Related Report
-
-
-
-
[Presentation] ネマリンミオパチーの新規原因遺伝子KLHL40 の同定2013
Author(s)
宮武 聡子, 輿水 江里子, 林 由起子, Gianina Ravenscroft, 三宅 紀子, 土井 宏, 鶴崎 美徳, 才津 浩智, 小坂 仁, 山下 純正, 大宅 喬, 増澤 祐子, 今村 伸太朗, 山下 倫明, 椎名 政昭, 緒方 一博, 西野 一三, Nigel Laing, 松本 直通
Organizer
日本人類遺伝学会第58回大会
Place of Presentation
江陽グランドホテル (宮城県仙台市)
Related Report
-