| Project/Area Number |
11670665
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kanazawa University |
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Principal Investigator |
SHIMIZU Masami Kanazawa University, Graduate School of Medical Science, Associate Professor, 大学院・医学系研究科, 助教授 (20183402)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Cardiac troponin I / Mutation / Hypertrophic cardiomyopathy |
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| Research Abstract |
We examined 270 consecutive unrelated probands with hypertrophic cardiomyopathy (HCM) who underwent genetic analysis, a 12-lead electrocardiography (ECG), and echocardiography. Informed consent was obtained from all subjects or from the parents of minors participating in the study.
DNA was isolated from peripheral white blood cells of all subjects. In vitro amplification of genomic DNA was performed via polymerase chain reaction. Single-strand conformational polymorphism (SSCP) analysis of amplified DNA was then performed. For abnormal SSCP pattern, DNA sequences were determined by the Dye Terminator Cycle Sequencing method using an automated fluorescent sequencer. The lysine 183 deletion (K183del) mutation in the cardiac troponin I (cTnl) gene was identified in 10 of 270 probands with HCM. Family members of the affected probands were evaluated similarly after informed consent was obtained.
In the carrier subjects, ECG abnormalities were initially noted during the early teenage years. Abnormal Q waves were found first and were frequently observed in leads II, III, aVF, V5 and V6 in teenage patients. On the other hand, wall hypertrophy became noticeable only in their late teens, and echocardiographic abnormalities appeared later than ECG abnormalities. HCM caused by the K183del mutation in the cTnl gene has a high disease penetrance in subjects over 20 years of age. About 30% of patients with HCM caused by a K183del mutation in the cTnl gene developed systolic dysfunction after 40 years of age. The change in interventricular septal thickness and the change in % fractional shortening were significantly correlated.
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