title: The cardiac sodium channel mutation delQKP 1507-1509 is associated with the expanding phenotypic spectrum of LQT3, conduction disorder, dilated cardiomyopathy, and high incidence of youth sudden death.
abstract: OBJECTIVE
  We report diverse phenotypic consequences of the delQKP-1507-1509 cardiac sodium channel mutation in three generations of a Chinese family.
  
  
  RESULTS
  Clinical and electrocardiographic (ECG), echocardiographic examination was followed by direct sequencing of SCN5A, KCNQ1, HERG, and LAMIN A/C to screen genomic DNA from blood samples. Of two mutation carriers, the proband was born with conduction disorders including second-degree atrioventricular (AV) block with prolonged QTc interval, additionally showing left anterior fascicular block (LAFB), incomplete right bundle-branch block (IRBBB), and intermittent third-degree AV block at 2 years, and clinical presentations of multiple syncope despite normal electroencephalograms at 8 years. Continuous ECG monitoring following presentation at 13 years revealed prolonged QTc and biphasic T-waves, multiple episodes of ventricular tachycardia, ventricular fibrillation, and torsades de pointes. Transthoracal echocardiography then revealed left ventricular dilatation and reduced systolic function. Another mutation carrier showed features of long QT syndrome type 3 (LQT3), LAFB, and dilated cardiomyopathy (DCM). Two additional subjects died suddenly at 13 and 33 years.
  
  
  CONCLUSIONS
  This data compliments and expands the spectrum of phenotypes resulting from this known gain-of-function mutation, including not only LQT3, cardiac conduction defects, and sudden death but also DCM, hitherto associated with loss-of-function mutations, for the first time.
authors.affiliation: 1Department of Paediatrics, First Affiliated Hospital, Cardiovascular Ion Channel Disease Laboratory, Medical College of Xi'an Jiaotong University, Xi'an, Peoples Republic of China.
authors.forename: Ruiming
authors.initials: R
authors.lastname: Shi
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Xihui
authors.initials: X
authors.lastname: Zhou
authors.forename: Hua
authors.initials: H
authors.lastname: Qiang
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Grace
authors.forename: Christopher L-H
authors.initials: CL
authors.lastname: Huang
authors.forename: Aiqun
authors.initials: A
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D053840:Brugada Syndrome / Q000235:genetics* / Q000401:mortality*; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000401:mortality*; D002681:China / Q000453:epidemiology; D003645:Death, Sudden / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome
chemical_list: D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels