title: Coexistence of Andersen-Tawil Syndrome with Polymorphisms in hERG1 Gene (K897T) and SCN5A Gene (H558R) in One Family.
abstract: BACKGROUND
  Andersen-Tawil Syndrome (ATS) is a channelopathy caused by mutations in KCNJ2 gene. It is characterized by symptoms of ventricular arrhythmias, periodic paralysis or muscle weakness, and dysmorphic features. ATS can present with the triad of symptoms, any combination or none of them. Risk factors for dangerous arrhythmias are unknown. The study assessed the impact of K897T polymorphism in hERG1 gene and H558R polymorphism in SCN5A gene coexisting with R218Q mutation in KCNJ2 in one family on clinical manifestation.
  
  
  METHODS
  Family members underwent clinical assessment, ECG and genotyping. Holter monitoring was performed in mutation carriers and additionally in one family member with no mutation, but with K897T polymorphism.
  
  
  RESULTS
  Proband with ATS mutation, K897T and H558R polymorphisms and proband's sister with ATS mutation and K897T polymorphism presented following symptoms: loss of consciousness, bidirectional and polymorphic ventricular tachycardia and about 5000 ventricular extrasystoles. Symptoms presented by the member with only the ATS mutation and by member with ATS mutation and H558R polymorphism were not as severe. U wave appeared in all examined family members regardless of the mutation presence. Studied individuals with ATS mutation had the T-peak-U-peak interval longer than 200 ms. In all ATS mutation carriers it was longer than in family members with no mutation. T-peak-T-end interval was the longest (>120 ms) in members with coexisting mutation and K897T polymorphism.
  
  
  CONCLUSIONS
  ATS severity possibly depends on other genes' polymorphisms. In the presented family, it could depend on the presence of K897T polymorphism in hERG1.
authors.affiliation: Student Research Group, Institute of Cardiology, Warsaw, Poland.
authors.forename: Michalina
authors.initials: M
authors.lastname: Jagodzińska
authors.affiliation: Department of Molecular Biology, Institute of Cardiology, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Szperl
authors.affiliation: Department of Molecular Biology, Institute of Cardiology, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ponińska
authors.affiliation: Department of Molecular Biology, Institute of Cardiology, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kosiec
authors.affiliation: Medical Center "Gajda-Med", Pułtusk, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Gajda
authors.affiliation: Department of Cardiology and Internal Medicine, Specialist Hospital, Gorlice, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kukla
authors.affiliation: Department of Congenital Cardiac Defects, Institute of Cardiology, Warsaw, Poland.
authors.forename: Elżbieta Katarzyna
authors.initials: EK
authors.lastname: Biernacka
mesh_terms: D050030:Andersen Syndrome / Q000235:genetics*; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
keywords: clinical; electrophsiology-long QT syndrome; molecular biology/genetics basic