title: Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen.
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.
authors.affiliation: Clinical and Molecular Genetics Unit, Institute of Child Health, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Tyson
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: M
authors.initials: M
authors.lastname: McEntagart
authors.forename: L A
authors.initials: LA
authors.lastname: Larsen
authors.forename: M
authors.initials: M
authors.lastname: Christiansen
authors.forename: M L
authors.initials: ML
authors.lastname: Whiteford
authors.forename: J
authors.initials: J
authors.lastname: Bathen
authors.forename: B
authors.initials: B
authors.lastname: Aslaksen
authors.forename: S J
authors.initials: SJ
authors.lastname: Sørland
authors.forename: O
authors.initials: O
authors.lastname: Lund
authors.forename: M E
authors.initials: ME
authors.lastname: Pembrey
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: M
authors.initials: M
authors.lastname: Bitner-Glindzicz
mesh_terms: D019943:Amino Acid Substitution; D004562:Electrocardiography; D005190:Family; D016368:Frameshift Mutation; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000235:genetics* / Q000503:physiopathology; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D009664:Norway; D018807:Polymorphism, Single-Stranded Conformational; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D017433:Protein Structure, Secondary; D006113:United Kingdom; D044465:White People
chemical_list: D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated