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Variants of the Lamin A/C (LMNA) Gene in Non-Valvular Atrial Fibrillation Patients.
- Source :
- Molecular Diagnosis & Therapy; 2012, Vol. 16 Issue 2, p99-107, 9p
- Publication Year :
- 2012
-
Abstract
- Background and Objective: Lamin A/C (LMNA) gene mutations cause dilated cardiomyopathy, often accompanied by conduction disturbances. Our aim was to search for LMNA mutations in individuals with atrial fibrillation. Methods: A cohort of Polish subjects (N = 103) with non-valvular atrial fibrillation with a high (48.5%) prevalence of conduction system disturbances was screened for LMNA variants by direct DNA sequencing. Results: We found a single non-synonymous variant (Thr528Met) in a 72-year-old patient with normal left ventricular function and episodes of advanced atrioventricular block. One of his two mutation-carrying daughters had episodes of type I second-degree atrioventricular block on a 24-hour Holter ECG and peak exercise arrhythmia. Interpretation of cardiac anomalies observed in the other daughter was complicated by thyroid insufficiency. A Thr528Met weak pathogenic effect was supported by transient transfections of C2C12 mouse myoblasts and computationally. Another interesting variant was Ile26Ile (c.78C>T), found in a New York Heart Association class III patient with a depressed left ventricular ejection fraction (30%), left bundle branch block, and a family history of heart disease. Ile26Ile was absent in 246 healthy individuals and was computationally predicted to interfere with splicing. Conclusion: LMNA mutations are not a frequent cause of atrial fibrillation even when conduction disease is present. Unlike the majority of LMNA mutations clearly associated with a severe clinical phenotype and a poor prognosis, Thr528Met results in a more subtle pathogenic effect, while Ile26Ile should be considered as a variant of unknown significance. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 11771062
- Volume :
- 16
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Molecular Diagnosis & Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 82337216
- Full Text :
- https://doi.org/10.1007/BF03256434