Key result
Familial AF shows no linkage to chromosome 10q22-q24, establishing genetic heterogeneity.
Why the study?
Atrial fibrillation is not generally regarded as heritable, but the genetic heterogeneity and familial basis of AF remain unclear.
Is familial atrial fibrillation a genetically heterogeneous disorder beyond the previously mapped chromosome 10 locus?
Observational (n=2,610)
No
Is familial atrial fibrillation a genetically heterogeneous disorder beyond the previously mapped chromosome 10 locus?
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“These data indicate that familial AF is genetically heterogeneous and that at least two disease genes are responsible for this disorder”
“may indicate two distinct mechanisms (and corresponding genes or pathways) involved in the origin of AF”
Familial atrial fibrillation is more common than previously recognized and is genetically heterogeneous, with mutations outside the initially identified chromosome 10 locus.
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.
No takes yet. Share an insight, caveat, or question.
Darbar et al. (2003) conducted an observational in Familial atrial fibrillation (n=2,610). Genetic linkage analysis (chromosome 10q22-q24 locus) was evaluated on Linkage of familial AF to the chromosome 10q22-q24 locus. Genetic linkage analysis in four families with autosomal dominant atrial fibrillation excluded linkage to the chromosome 10q22-q24 region, establishing that the disorder is genetically heterogeneous.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: