[Genetics of hereditary cardiopathies]. / Génétique des cardiopathies héréditaires.

Hypertrophic cardiomyopathy may be secondary to a mutation in the cardiac beta myosin heavy chain (14q11-q12), alpha tropomyosin (15q22), troponin T (1q32), protein C gene (11p11-q13) or in a non yet mapped gene. A X-linked dilated cardiomyopathy may be due to a mutation in the dystrophin gene (Xp21). The long QT syndrome may be secondary to a mutation in a potassium channel (7q35-36), an alpha subunit of the sodium channel gene (3p21) or in genes not yet identified (11p15.5, 4q25-q27). Marfan syndrome is associated to mutations in the fibrillin 1 gene (15q21.1) and a Marfan-like syndrome with not ocular anomalies was mapped to 3p24. Patients with Williams-Beuren syndrome have microdeletions in 7q11, whereas in the supravalvular aortic stenosis, the elastin gene which maps to the same region, is mutated. In Di George and Shprintzen syndromes but not in conotruncal malformations, microdeletions in 22q11 are observed. Heterotaxia can be transmitted by 3 types of mendelian inheritance (Xq24-q27.1). Finally, other diseases were mapped: Noonan and Holt-Oram syndromes (12q), isolated conduction blocks (19q13.3), arrhythmogenic right ventricular cardiomyopathy (14q23-q24), total anomalous pulmonary venous return (4p13-q12) and Osler-Weber-Rendu (9q33-q34.1, 3p22 and 12q1). In the near future, these incoming data will deeply modify the cardiovascular field.

An isolated cardiac conduction disease maps to chromosome 19q.

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 (< or = -30 or > or = +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.