Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen

Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive syndrom e characterised by profound congenital sensorineural deafness and prolongat ion of the QT interval on the electrocardiogram, representing abnormal vent ricular repolarisation. In a study of ten British and Norwegian families wi th JLNS, we have identified all of the mutations in the KCNQ1 gene, includi ng two that are novel. Of the nine mutations identified in this group of 10 families, five are nonsense or frameshift mutations. Truncation of the pro tein proximal to the recently identified C-terminal assembly domain is expe cted to preclude assembly of KCNQ1 monomers into tetramers and explains the recessive inheritance of JLNS. However, study of a frameshift mutation, wi th a dominant effect phenotypically, suggests the presence of another assem bly domain nearer to the N-terminus.