Correspondence

Familial Atrial Fibrillation

N Engl J Med 1997; 337:350July 31, 1997

Article

To the Editor:

Brugada et al. (March 27 issue)1 reported the mapping of familial atrial fibrillation in three kindreds to a locus on chromosome 10q, but they did not discuss the locus on 10q for dilated cardiomyopathy with mitral-valve prolapse, which they and others have previously described.2 Supraventricular dysrhythmias and dilated cardiomyopathy often segregate within the same family, apparently as a result of variable expression of a single trait.3 Mitral-valve prolapse itself is associated with ventricular and supraventricular dysrhythmias.4 Interestingly, two of the affected family members in the study of familial atrial fibrillation had evidence of ventricular dilatation and systolic dysfunction.

Many clinical entities in cardiovascular disease are so heterogeneous that they confound investigation. It would be central to the message of this paper to know whether or not the loci for atrial fibrillation and dilated cardiomyopathy are genetically distinct. In addition, was there any clinical information — for example, from endomyocardial biopsy — to link the two phenotypes? Clinical genetics and molecular genetics offer at least some insight into the inadequacies of current nosology.

Calum A. MacRae, M.B., Ch.B.
Brigham and Women's Hospital, Boston, MA 02115

4 References

1. 1

   Brugada R, Tapscott T, Czernuszewicz GZ, et al. Identification of a genetic locus for familial atrial fibrillation. N Engl J Med 1997;336:905-911
   Full Text | Web of Science | Medline

2. 2

   Bowles KR, Gajarski R, Porter P, et al. Gene mapping of familial autosomal dominant dilated cardiomyopathy to chromosome 10q21-23. J Clin Invest 1996;98:1355-1360
   CrossRef | Web of Science | Medline

3. 3

   Kass S, MacRae C, Graber HL, et al. A gene defect that causes conduction system disease and dilated cardiomyopathy maps to 1p1-1q1. Nat Genet 1994;7:546-551
   CrossRef | Web of Science | Medline

4. 4

   Kligfield P, Hochreiter C, Kramer H, et al. Complex arrhythmias in mitral regurgitation with and without mitral valve prolapse: contrast to arrhythmias in mitral valve prolapse without mitral regurgitation. Am J Cardiol 1985;55:1545-1549
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Roberts replies:

To the Editor: My colleagues and I appreciate Dr. MacRae's comments about a possible relation between the locus for dilated cardiomyopathy and the locus for atrial fibrillation, since the two are in overlapping regions of chromosome 10q (10q21–23 and 10q22–24, respectively). We do not think there is any relation between dilated cardiomyopathy and atrial fibrillation in the family with atrial fibrillation that we studied. We have now identified several other families with atrial fibrillation with members as old as 70 and 80, and there is no evidence of dilated cardiomyopathy in these patients. It is also noteworthy that in the family with atrial fibrillation studied by us, the condition began in some members when they were as young as two or three years old. In the family with dilated cardiomyopathy, there was no atrial fibrillation. We have no evidence to indicate that the locus for atrial fibrillation at 10q22–24 is in any way related to the locus for dilated cardiomyopathy at 10q21–23, even though they are on the same chromosome. The actual physical distance between these two loci (as opposed to the estimated genetic distance) is potentially several million base pairs and represents hundreds of genes. However, the possibility that these diseases are due to different alleles of the same gene cannot be ruled out until the gene or genes have been identified.

Robert Roberts, M.D.
Baylor College of Medicine, Houston, TX 77030

Citing Articles (3)

Citing Articles

1. 1

   James K. Liao. (2010) Rac1 and Connective Tissue Growth Factor. Journal of the American College of Cardiology 55:5, 481-482
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2. 2

   Florence Rothenberg, Michiko Watanabe, Benjamin Eloff, David Rosenbaum. (2005) Emerging patterns of cardiac conduction in the chick embryo: Waveform analysis with photodiode array-based optical imaging. Developmental Dynamics 233:2, 456-465
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3. 3

   Ludwig Thierfelder. (1998) Genetik der dilatativen Kardiomyopathie. Medizinische Klinik 93:4, 210-214
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