title: Novel KCNQ1 mutations associated with recessive and dominant congenital long QT syndromes: evidence for variable hearing phenotype associated with R518X.
abstract: Congenital long QT syndrome may be transmitted as either an autosomal dominant or recessive trait. Two families with the autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS), and one family with the autosomal dominant Romano-Ward syndrome (RWS) were evaluated for mutations in KCNQ1. Two different novel frameshift mutations were discovered in one of the JLNS families (1188delC) and in the RWS family (504delG). A third allele (R518X) was observed in the second JLNS family. The R518X allele was previously associated with recessive long QT syndrome without deafness, but was present in a congenitally deaf proband in our study. These data extend the range of known KCNQ1 mutations associated with both recessive and dominant forms of congenital long QT syndrome, and demonstrate that the R518X allele may be associated with or without congenital deafness.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wei
authors.forename: F A
authors.initials: FA
authors.lastname: Fish
authors.forename: R J
authors.initials: RJ
authors.lastname: Myerburg
authors.forename: D M
authors.initials: DM
authors.lastname: Roden
authors.forename: A L
authors.initials: AL
authors.lastname: George
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics*; D005808:Genes, Recessive / Q000235:genetics*; D006309:Hearing / Q000235:genetics*; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000151:congenital* / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated
chemical_list: D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated