Structural analysis of obscurin gene in hypertrophic cardiomyopathy.
Biochem Biophys Res Commun
; 362(2): 281-7, 2007 Oct 19.
Article
in En
| MEDLINE
| ID: mdl-17716621
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cardiomyopathy, Hypertrophic
/
Guanine Nucleotide Exchange Factors
/
Muscle Proteins
/
Mutation
Type of study:
Prognostic_studies
Limits:
Adult
/
Animals
/
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2007
Document type:
Article
Affiliation country:
Japan