Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen |
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Authors: | Jessica Tyson Lisbeth Tranebjærg Meriel McEntagart Lars Larsen Michael Christiansen Margo Whiteford Jørn Bathen Bjørn Aslaksen Svein Sørland Ole Lund Marcus Pembrey Sue Malcolm Maria Bitner-Glindzicz |
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Affiliation: | Clinical and Molecular Genetics Unit, Institute of Child Health, London, UK. |
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Abstract: | Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive syndrome characterised by profound congenital sensorineural deafness and prolongation of the QT interval on the electrocardiogram, representing abnormal ventricular repolarisation. In a study of ten British and Norwegian families with JLNS, we have identified all of the mutations in the KCNQ1 gene, including two that are novel. Of the nine mutations identified in this group of 10 families, five are nonsense or frameshift mutations. Truncation of the protein proximal to the recently identified C-terminal assembly domain is expected to preclude assembly of KCNQ1 monomers into tetramers and explains the recessive inheritance of JLNS. However, study of a frameshift mutation, with a dominant effect phenotypically, suggests the presence of another assembly domain nearer to the N-terminus. |
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