gms | German Medical Science

33. Internationale Konferenz für Elektrokardiographie

Internationale Konferenz für Elektrokardiographie

A locus for autosomal dominant sinus node disease is mapped on chromosome 7q21.3-q31.2

Meeting Abstract

  • corresponding author presenting/speaker D. Etzrodt - Interdisciplinary Centre for Clinical Research, Münster, Germany
  • S. Rust - Leibniz Institute for Arteriosclerosis Research, Münster, Germany
  • G. Breithardt - Department of Cardiology and Angiology, Münster, Germany
  • E. Schulze-Bahr - Department of Cardiology and Angiology, Münster, Germany

33rd International Congress on Electrocardiology. Cologne, 28.06.-01.07.2006. Düsseldorf, Köln: German Medical Science; 2007. Doc06ice063

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Veröffentlicht: 8. Februar 2007

© 2007 Etzrodt et al.
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Question: Sinusnode disease (SND) is a frequent cardiac arrhythmia. In one-third, the disease is idiopathic. SND is associated with a spectrum of phenotypes, like sinus bradycardia, SA block/arrest, atrial fibrillation and others. Mutations in the HCN4 and SCN5A gene have been identified as a genetic cause for SND. Here, we report about a family with autosomal dominant sinuatrial disease and the results of a linkage analysis to identify the disease locus.

Method used: A three-generation family (n=25 members) with SND was clinically characterized. DNA was extracted from EDTA-blood and genome-wide linkage analysis was done using the mapping set LMS-MD-10 (Applied Biosystems). Lod score calculations were performed using FASTLINK version of the LINKAGE 5.1 program package and MLINK. Furthermore, we sequenced 20 candidate genes. A Follow-up fine mapping with the SNP Mapping 500K Array Set (Affymetrix) was carried out to search for deletions.

Results: In 10 affected family members were no extrinsic causes for sinuatrial abnormalities detectable. Two adult patients required pacemaker implantation. No sudden cardiac death is known. Two-point analysis showed significant evidence of linkage to multiple markers between D7S491 and D7S2502. Multipoint linkage analysis in this region demonstrated seven markers with a positive LOD score above 3.0. The maximum multipoint LOD score of 4.6 (theta=0) was obtained within marker D7S491 until D72460 and 3.9 within marker D7S821 and D7S491. Sequencing of candidate genes did not identify a concrete gene.The combined loss of heterozygosity - and copy number analysis of SNP chip data is currently in process.

Conclusion: These data support an additional disease locus for sinuatarial disease being located on chromosome 7q21.3-q31.2 (D7S821 - D72460, 16.8cM). These results let assume that SND is a genetically heterogeneous disease, like most other arrhytmias. Identifying the gene will give further light into pathomechanisms of SND.