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Genetic investigation of gap junction protein, alpha 5 of in Russian families with sick sinus syndrome

Connexin 40 (Cx40) is a gap-junction protein expressed in the heart where it mediates the coordinated electrical activation of the atria and ventricular conduction tissues, facilitates cell-to-cell adhesion, and provides pathways for direct intercellular communication. Recent studies have shown that Cx40 null mice have cardiac conduction abnormalities with a very high incidence of cardiac malformations in heterozygous (18%) and homozygous (33%) animals, indicating that Cx40 plays a vital role in cardiomorphogenesis.The process that mediates interactions between an AV node cell and its surroundings that contributes to the process of the AV node cell communicating with a bundle of His cell in cardiac conduction. Encompasses interactions such as signaling or attachment between one cell and another cell, between a cell and an extracellular matrix, or between a cell and any other aspect of its environment. 

This first study of SSS in a Russian population comprises the clinical and genetic investigation of 30 Russian families, including 67 members. The involvement of the Cx40 genes was investigated. The control group consisted of 615 patients without clinical ECG manifestations of cardiac diseases. All the examinees have undergone ECG, echocardioscopy, electrophysiological examination of the heart. 

We conclude that polymorphism 44AG has mutation-specific effects on Cx40-related SSS. 

Mutation Cx40 impairs gap junction formation at cell-cell interfaces. This is the first demonstration of a germ line mutation in a connexin gene that emphasizes the importance of Cx40 in normal propagation in the specialized conduction system. 

This study provides further evidence of the genetic heterogeneity of SSS.