Familial atrial fibrillation is a genetically heterogeneous disorder

Dawood Darbar, Kathleen J. Herron, Jeffrey D. Ballew, Arshad Jahangir, Bernard J. Gersh, Win K. Shen, Stephen C. Hammill, Douglas L Packer, Timothy Mark Olson

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2185-2192
Number of pages8
JournalJournal of the American College of Cardiology
Volume41
Issue number12
DOIs
StatePublished - Jun 18 2003

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Atrial Fibrillation
Chromosomes, Human, Pair 10
Chromosomes
Lamin Type A
Inborn Genetic Diseases
Genetic Loci
Dilated Cardiomyopathy
Cardiomyopathies
Genetic Markers
Medical Records
Disease Progression
Cardiac Arrhythmias
History

ASJC Scopus subject areas

  • Nursing(all)

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Familial atrial fibrillation is a genetically heterogeneous disorder. / Darbar, Dawood; Herron, Kathleen J.; Ballew, Jeffrey D.; Jahangir, Arshad; Gersh, Bernard J.; Shen, Win K.; Hammill, Stephen C.; Packer, Douglas L; Olson, Timothy Mark.

In: Journal of the American College of Cardiology, Vol. 41, No. 12, 18.06.2003, p. 2185-2192.

Research output: Contribution to journalArticle

Darbar, D, Herron, KJ, Ballew, JD, Jahangir, A, Gersh, BJ, Shen, WK, Hammill, SC, Packer, DL & Olson, TM 2003, 'Familial atrial fibrillation is a genetically heterogeneous disorder', Journal of the American College of Cardiology, vol. 41, no. 12, pp. 2185-2192. https://doi.org/10.1016/S0735-1097(03)00465-0
Darbar, Dawood ; Herron, Kathleen J. ; Ballew, Jeffrey D. ; Jahangir, Arshad ; Gersh, Bernard J. ; Shen, Win K. ; Hammill, Stephen C. ; Packer, Douglas L ; Olson, Timothy Mark. / Familial atrial fibrillation is a genetically heterogeneous disorder. In: Journal of the American College of Cardiology. 2003 ; Vol. 41, No. 12. pp. 2185-2192.
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abstract = "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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AU - Darbar, Dawood

AU - Herron, Kathleen J.

AU - Ballew, Jeffrey D.

AU - Jahangir, Arshad

AU - Gersh, Bernard J.

AU - Shen, Win K.

AU - Hammill, Stephen C.

AU - Packer, Douglas L

AU - Olson, Timothy Mark

PY - 2003/6/18

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N2 - 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.

AB - 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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