A NOVEL MUTATION IN THE POTASSIUM CHANNEL GENE KVLQT1 CAUSES THE JERVELL AND LANGE-NIELSEN CARDIOAUDITORY SYNDROME

The Jervell and Lange-Nielsen (JLN) syndrome (MIM 220400) is an inheri ted autosomal recessive disease characterized by a congenital bilatera l deafness associated with a QT prolongation on the electrocardiogram, syncopal attacks due to ventricular arrhythmias and a high risk of su dden death(1). JLN syndrome is a rare disease, which seems to affect l ess than one percent of all deaf children(2-4) Linkage to chromosome 1 1p15.5 markers was found by analysing four consanguinous families. Rec ombinants allowed us to map the JLN gene between D11S922 and D11S4146, to a 6-cM interval where KVLQT1, a potassium channel gene causing Rom ano-Ward (RW) syndrome, the dominant form of long QT syndrome, has bee n previously localized(5), An homozygous deletion-insertion event (124 4, -7 +8) in the C-terminal domain of this gene was detected in three affected children of two families. We found that KVLQT1 is expressed i n the stria vascularis of mouse inner ear by in situ hybridization. Ta ken together, our data indicate that KVLQT1 is responsible for both JL N and RW syndromes and has a key role not only in the ventricular repo larization but also in normal hearing, probably via the control of end olymph homeostasis.