2014 Fiscal Year Final Research Report
Identification and functional analysis of a new candidate gene of nemaline myopathy
Project/Area Number |
25860876
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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 |
IMAMURA Eriko 横浜市立大学, 医学(系)研究科(研究院), 博士研究員 (80637877)
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Keywords | 先天性ミオパチー / エクソーム解析 / ゼブラフィッシュ |
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.
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Free Research Field |
遺伝学
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