thee long QT syndrome (LQT) is a familial predisposition to sudden death from cardiac arrhythmias. M. Keating et al. performed linkage analysis in a large Utah family and found that th disease was closely linked to the Harvey ras-1 (H-ras-1) locus on chromosome 11. With the use of the probe pTBB-2 at the H-ras-1 oncogene, a logarithm of the likelihood ratio for linkage (lod score) of +16.44 was obtained by Keating et al. In a subsequent study, tight linkage of LQT to the H-ras-1 locus was found in six other small LQT families. The combined lod score from these two studies was +21.65 at a recombination fraction of 0. This tight linkage suggests that mutations at the H-ras-1 locus or at a closely linked locus resulted in LQT in the families studied. In view of the clinical heterogeneity and possible genetic heterogeneity in this syndrome, we analyzed a large Jewish family with a history of LQT. This family, whose origin is the island of Jerba near Tunic and whose members reside in Israel, is probably the largest family with LQT outside the United States. It comprises 131 individuals, of whom 28 have been affected. Clinical and electrocardiographic data collected overmore » 7 years were available for 92 family members and blood samples for genetic analysis were available for 74. This analysis, together with that of Keating et al., provides evidence for genetic heterogeneity in the determination of the LQT.« less