An Isolated Cardiac Conduction Disease Maps to Chromosome 19q

• Published in: Circulation research Vol. 77; no. 4; pp. 735 - 740
• Main Authors: de Meeus, Anne, Stephan, Edouard, Debrus, Sophie, Jean, Marie-Kamala, Loiselet, Jacques, Weissenbach, Jean, Demaille, Jacques, Bouvagnet, Patrice
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.10.1995; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Base Sequence; Biological and medical sciences; Biomarkers; Cardiology. Vascular system; Chromosome Mapping; Chromosomes, Human, Pair 19 - genetics; Congenital heart diseases. Malformations of the aorta, pulmonary vessels and vena cava; Death, Sudden, Cardiac; Family; Genetic Linkage; Heart; Heart Block - genetics; Heart Conduction System - physiopathology; Humans; Medical sciences; Molecular Sequence Data; Genetic mapping; Heart; Human; Chromosome 19; Genetic inheritance; Arrhythmia; Genetic marker; Sudden death; Cardiovascular disease; Conduction disorder; Genetic disease; Heart disease; Autosomal character; Localization
• DOI: 10.1161/01.res.77.4.735
• ISSN: 0009-7330

Isolated cardiac conduction disease is an autosomal dominant defect that includes various combinations of bundle branch or fascicular blocks. These defects can cause sudden death due to a complete heart block. We used a genome-wide screening approach with polymorphic (CA)n repeat markers to determine the chromosomal position of the gene defect implicated in this disorder. The analyses were carried out on a large Lebanese kindred, which included individuals with either a complete or incomplete right bundle branch block (RBBB) with a vertical-axis deviation (less than equals minus 30 or more than equals plus 100). Linkage to the disease locus was detected with the polymorphic marker D19S604 on the q arm of chromosome 19 (19q13.3) with a multipoint lod score of 7.18. Additionally, we were able to exclude the flanking loci D19S606 and D19S571, which are 13 cM apart because of recombination events in three affected individuals. The histidine-rich calcium-binding protein gene is found in this region and is an attractive candidate gene on the basis of its physiological properties and a tight linkage. There is no expansion in two exon 1 regions known for a variable number of triplet repeats.(Circ Res. 1995;77:735-740.)