Genetic factors that play a role in the aeti-ology of life-threatening cardiac arrhyth-mias have been identified during the last few years. One of these genes, coding for a putative potassium channel KVLQT1, maps to chromosome 11p15 near the IGF2 gene", in a region associated with an over-growth malformation disorder called the Beckwith-Wiedemann syndrome (BWS). Until recently, KVLOT1 was known as one of the genes that cause the long QT syndrome (LQT, type Romano Ward), a cardiac arrhythmia that is dominantly inherited. In this issue of Nature Genetics, two papers describe novel features for this gene, one of which is quite unexpected. Neyroud et alº show that KVLOT1 is involved in the development of the Jervell and Lange-Nielsen cardioauditory syn-drome (JLN), and, most remarkably, Lee et alº give evidence that KVLOT1 is imprint-ed in most tissues, with the exclusion of the heart, and that it might be involved in the development of BWS, a disorder that is clearly subject to imprinting. Cardiac arrhythmias, based on abnormal repolarization visualized as a prolonged QT interval on an ECG, can lead to sudden death, and in general account for approxi-mately 11% of all natural deaths. LQT syndrome has become the paradigm for the study of genetic factors in cardiac arrhyth-mias. Genetic studies on LQT have shown that genes coding for ion channels are responsible for the prolonged QT interval. The syndrome is genetically heteroge-neous, including the following genes": the cardiac sodium channel gene (SCN5A) on chromosome 3p21; the human Ether-a-gogo related gene (HERG) on chromosome 7q35-36 encoding the IKr current; the KVLOT1 gene on chromosome 11p15. 5 that creates a functional potassium channel together with the Isk protein (minK gene on chromosome 21); an unknown gene on chromosome 4 and additional unmapped genes. The various underlying genetic defects can be appreciated on the ECG since they give distinct ECG patterns". Treatment of these patients may become “gene-specific". JLN syndrome is a rare disease and is, like LQT syndrome, characterized by a prolonged QT interval and cardiac arrhythmia (that is, Torsade de pointes–polymorphous ventricular tachycardia leading to syncopal attacks or deteriorating into ventricular fibrillator and nature genetics volume 15 february 1997 sudden death). However, unlike LQT syn-drome, JLN is also associated with con-genital bilateral deafness and is inherited in an autosomal recessive way. Neyroud et alº studied four consanguineous families and found linkage to 11p15. 5 markers in a 6-cM region encompassing KVLOTI.(It should be noted that linkage of JLN to the llp 15.5 marker HRAS was previously excluded" either due to recombination with the more proximal KVLOTl gene or to genetic heterogeneity, as seen in LQT syndrome.) Neyroud and co-workers found a homozygous KVLOTI deletion-insertion mutation in two of these families demonstrating that mutant KVLQT1 can cause the JLN syndrome. In addition, they showed that KVLOT1 is expressed in the stria vascularis of mouse inner ear by in situ hybridization, which could explain the bilateral deafness via the control of endolymph homeostasis. Since all families were consanguineous, confirmation of their data in nonconsanguineous patients would be welcome. In particular, for the bilateral deafness, the genetic defect might be different from the KVLOTi gene. However, Vetter et al." showed in mice that the IsK gene is responsible for inner ear defects. Given that IsK and KVLOT1 form the functional potassium channel, it is not surprising that a mutation in either gene could have the same effect. It …