CLINICAL RESEARCH: ATRIAL FIBRILLATION/FLUTTER, TACHYCARDIA
Familial atrial fibrillation is a genetically heterogeneous disorder
Dawood Darbar, MD*,
Kathleen J. Herron, BA*,
Jeffrey D. Ballew, MSc*,
Arshad Jahangir, MD*,
Bernard J. Gersh, MBChB, DPhil, FACC*,
Win-K. Shen, MD, FACC*,
Stephen C. Hammill, MD, FACC*,
Douglas L. Packer, MD, FACC* and
Timothy M. Olson, MD* ,*
* Departments of Medicine, Division of Cardiovascular Diseases, Rochester, Minnesota, USA
Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota, USA
Manuscript received August 14, 2002;
revised manuscript received November 22, 2002,
accepted December 18, 2002.
* Reprint requests and correspondence: Dr. Timothy M. Olson, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
olson.timothy{at}mayo.edu
OBJECTIVES: The aims of this study were to identify and characterize familial cases of atrial fibrillation (AF) in our clinical practice and to determine whether AF is genetically heterogeneous.
BACKGROUND: Atrial fibrillation is not generally regarded as a heritable disorder, yet a genetic locus for familial AF was previously mapped to chromosome 10.
METHODS: Of 2,610 patients seen in our arrhythmia clinic during an 18-month study period, 914 (35%) were diagnosed with AF. Familial cases were identified by history and medical records review. Four multi-generation families with autosomal dominant AF (FAF 1 to 4) were tested for linkage to the chromosome 10 AF locus.
RESULTS: Fifty probands (5% of all AF patients; 15% of lone AF patients) were identified with lone AF (age 41 ± 9 years) and a positive family history (1 to 9 additional relatives affected). In FAF 1 to 3, AF was associated with rapid ventricular response. In contrast, AF in FAF-4 was associated with a slow ventricular response and, with progression of the disease, junctional rhythm and cardiomyopathy. Genotyping of FAF 1 to 4 with deoxyribonucleic acid markers spanning the chromosome 10q22-q24 region excluded linkage of AF to this locus. In FAF-4, linkage was also excluded to the chromosome 3p22-p25 and lamin A/C loci associated with familial AF, conduction system disease, and dilated cardiomyopathy.
CONCLUSIONS: Familial AF is more common than previously recognized, highlighting the importance of genetics in disease pathogenesis. In four families with AF, we have excluded linkage to chromosome 10q22-q24, establishing that at least two disease genes are responsible for this disorder.
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Abbreviations and Acronyms
| | AF | = atrial fibrillation | | cM | = centiMorgan | | DNA | = deoxyribonucleic acid | | ECG | = electrocardiogram/electrocardiographic/ electrocardiography | | FAF | = multi-generation families with autosomal dominant atrial fibrillation | | PCR | = polymerase chain reaction |
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