title: Identification of a novel KCNQ1 mutation associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long QT syndrome in a Chinese family.
abstract: BACKGROUND
  Long QT syndrome (LQTS) is a cardiac disorder characterized by prolonged QT intervals on electrocardiograms (ECG), ventricular arrhythmias, and sudden death. Clinically, two inherited forms of LQTS have been defined: autosomal dominant LQTS or Romano-Ward syndrome (RWS) not associated with deafness and autosomal recessive LQTS or Jervell and Lange-Nielsen syndrome (JLNS) associated with deafness.
  
  
  METHODS
  A Chinese family with both RWS and JLNS was identified. Family members were diagnosed based on the presence of a prolonged QT interval as seen on a 12-lead ECG and a medical history of syncope, palpitation, and deafness. Mutational studies in the KCNQ1 potassium channel gene were performed using direct DNA sequence analysis and restriction length polymorphism analysis.
  
  
  RESULTS
  The proband in the Chinese family and her brother had previously been diagnosed with JLNS, and two other members were affected with RWS. The proband was also affected with atrial fibrillation. A single nucleotide substitution of C to T at nucleotide 965 of KCNQ1 was identified, and the mutation resulted in the substitution of a threonine residue at codon 322 by a methionine residue (T322M). The novel heterozygous T322M mutation was identified in two patients with RWS, one member with borderline QTc, and two normal family members. The two JLNS patients in the family carried the homozygous T322M mutation. The T322M mutation was not found in 200 Chinese normal controls.
  
  
  CONCLUSIONS
  Our results suggest that T322M is a novel mutation that caused RWS with high intrafamilial variability in the heterozygous carriers and typical JLNS in the homozygous carriers within this Chinese family. The T322M mutation is the first mutation identified for JLNS in the Chinese population.
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, PR China. zhangsuhealth@126.com
authors.forename: Su
authors.initials: S
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Yin
authors.forename: Xiang
authors.initials: X
authors.lastname: Ren
authors.forename: Pengyun
authors.initials: P
authors.lastname: Wang
authors.forename: Shirong
authors.initials: S
authors.lastname: Zhang
authors.forename: Lingling
authors.initials: L
authors.lastname: Cheng
authors.forename: Junguo
authors.initials: J
authors.lastname: Yang
authors.forename: Jing Yu
authors.initials: JY
authors.lastname: Liu
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
authors.forename: Qing Kenneth
authors.initials: QK
authors.lastname: Wang
mesh_terms: D002675:Child, Preschool; D002681:China; D005260:Female; D006801:Humans; D029593:Jervell-Lange Nielsen Syndrome / Q000235:genetics*; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D029597:Romano-Ward Syndrome / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D051657:KCNQ1 Potassium Channel