2007年10月19日
Structural analysis of obscurin gene in hypertrophic cardiomyopathy.
Biochemical and biophysical research communications
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- 巻
- 362
- 号
- 2
- 開始ページ
- 281
- 終了ページ
- 7
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
Hypertrophic cardiomyopathy (HCM) is a cardiac disease characterized by left ventricular hypertrophy with diastolic dysfunction. Molecular genetic studies have revealed that HCM is caused by mutations in genes for sarcomere/Z-band components including titin/connectin and its associate proteins. However, disease-causing mutations can be found in about half of the patients, suggesting that other disease-causing genes remain to be identified. To explore a novel disease gene, we searched for obscurin gene (OBSCN) mutations in HCM patients, because obscurin interacts with titin/connectin. Two linked variants, Arg4344Gln and Ala4484Thr, were identified in a patient and functional analyses demonstrated that Arg4344Gln affected binding of obscurin to Z9-Z10 domains of titin/connectin, whereas Ala4484Thr did not. Myc-tagged obscurin showed that Arg4344Gln impaired obscurin localization to Z-band. These observations suggest that the obscurin abnormality may be involved in the pathogenesis of HCM.
- リンク情報
- ID情報
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- ISSN : 0006-291X
- PubMed ID : 17716621