Nature Genetics
15, 186 - 189 (1997)
doi:10.1038/ng0297-186
A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndromeNathalie Neyroud1, 2, *, Frédérique Tesson1, *, Isabelle Denjoy2, 3, Michel Leibovici4, Claire Donger1, Jacques Barhanin5, Sabine Fauré6, Françoise Gary6, Philippe Coumel2, Christine Petit4, Ketty Schwartz1
& Pascale Guicheney1, 7
1INSERM UR153, Groupe Hospitalier Pitié-Salpétrière, Institut de Myologie, 47 boulevard de l'Hôpital, 75013 Paris, France.
2Service de Cardiologie, Hôpital Lariboisière, 75010 Paris, France.
3Château des Côtes, LesLoges en josas, 78350 France.
4Unité de Génétique moléculaire, CNRS URA 1968, Institut Pasteur, 75015 Paris, France.
5Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 06560 Valbonne, France.
6Gènéthon-CNRS URA 1922, 91002 Evry, France.
*N.N. and F. T. contributed equally to this work.
7e-mail: pguichene@myologie.infobiogen.fr. The Jervell and Lange-Nielsen (JLN) syndrome (MIM 220400) is an inherited autosomal recessive disease characterized by a congenital bilateral deafness associated with a QT prolongation on the electrocardiogram, syncopal attacks due to ventricular arrhythmias and a high risk of sudden death1. JLN syndrome is a rare disease, which seems to affect less than one percent of all deaf children2−4. Linkage to chromosome 11p15.5 markers was found by analysing four consanguinous families. Recombinants allowed us to map the JLN gene between D115922 and D1154146, to a 6-cM interval where KVLQT1, a potassium channel gene causing Romano-Ward (RW) syndrome, the dominant form of long QT syndrome, has been previously localized5. An homozygous deletion-insertion event (1244, -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 in the stria vascularis of mouse inner ear by in situ hybridization. Taken together, our data indicate that KVLQT1 is responsible for both JLN and RW syndromes and has a key role not only in the ventricular repolarization but also in normal hearing, probably via the control of endolymph homeostasis.
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