title: Novel compound heterozygous mutations in the KCNQ1 gene associated with autosomal recessive long QT syndrome (Jervell and Lange-Nielsen syndrome).
abstract: BACKGROUND
  The Jervell and Lange-Nielsen syndrome (JLNS) is the autosomal recessive form of long QT syndrome (LQTS)--a familial cardiac disorder that causes syncope, seizures, and sudden death from ventricular arrhythmias, specifically torsade de pointes. JLNS is associated with sensorineural deafness and has been shown to occur with homozygous mutations in KCNQ1 or KCNE1 in JLNS families in which QTc prolongation is inherited as a dominant trait. This study investigated the molecular pathology of a family with clinical evidence of JLNS.
  
  
  RESULTS
  Single-strand conformation polymorphism, denaturing high performance liquid chromatography, and DNA sequencing analyses were used to screen for KCNQ1 mutations. Novel compound heterozygous nonsense mutations R518X/Q530X in the C-terminus of KCNQ1 were identified in both affected dizygotic twins; both the parents and a sibling each carried only one of the mutant alleles and were asymptomatic with modestly prolonged QTc intervals (0.46, 0.50, and 0.45 seconds, respectively). These two nonsense mutations lead to premature termination of C-terminus with truncation of the postulated assembly domain.
  
  
  CONCLUSIONS
  Novel compound heterozygous nonsense mutations in C-terminus of KCNQ1 can cause JLNS.
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D004200:Diseases in Twins / Q000235:genetics; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D017422:Sequence Analysis, DNA; D013223:Statistics as Topic
chemical_list: D005819:Genetic Markers; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated