Cardiac Myosin Light Chain Kinase Mutation as a Cause of Cardiomyopathies

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790748
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Kanazawa University
• Principal Investigator: KONNO Tetsuo 金沢大学, 医学系, 助教 (50377389)
• Co-Investigator(Renkei-kenkyūsha): KITAKAZE Masafumi 独立行政法人国立循環器病研究センター, 臨床研究開発部, 部長 (20294069) ; TAKASHIMA Seiji 大阪大学, 大学院生命機能研究科, 教授 (90379272) ; YAMAZAKI Satoru 独立行政法人国立循環器病研究センター, 細胞生物学部細胞形態研究室, 室長 (70348796) ; SEGUCHI Osamu 独立行政法人国立循環器病研究センター, 病院移植部, 研究員 (60570869)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: genetics / cardiomyopathy / heart failure

Outline of Final Research Achievements

Recently, cardiac myosin light chain kinase (cMLCK) was cloned from the myocardia of patients with heart failure, although it is unknown whether mutations in cMLCK gene (MYLK3) causes cardiomyopathies. We identified a missense and deletion variant in hypertrophic cardiomyopathy (HCM) and in dilated cardiomyopathy (DCM), respectively. In vitro kinase assay demonstrated enhanced kinase activity in the missense mutant protein, while diminished activity in deletion mutant protein. Whole exome sequencing showed absence of known DCM causing mutations in pedigrees harboring the mutation. These findings suggest that enhanced cMLCK activity may cause HCM, while declined cMLCK activity may cause DCM. Our data will provide the new insights into mechanisms responsible for cardiomyopathies.

Free Research Field

循環器内科学、心不全