The genetic basis of long QT and short QT syndromes: a mutation update.
Long QT and short QT syndromes (LQTS and SQTS) are cardiac repolarization abnormalities that are characterized by length perturbations of the QT interval as measured on electrocardiogram (ECG). Prolonged QT interval and a propensity for ventricular tachycardia of the torsades de pointes (TdP) type are characteristic of LQTS, while SQTS is characterized by shortened QT interval with tall peaked T-waves and a propensity for atrial fibrillation. Both syndromes represent a high risk for syncope and sudden death. LQTS exists as a congenital genetic disease (cLQTS) with more than 700 mutations described in 12 genes (LQT1-12), but can also be acquired (aLQTS). The genetic forms of LQTS include Romano-Ward syndrome (RWS), which is characterized by isolated LQTS and an autosomal dominant pattern of inheritance, and syndromes with LQTS in association with other conditions. The latter includes Jervell and Lange-Nielsen syndrome (JLNS), Andersen syndrome (AS), and Timothy syndrome (TS). The genetics are further complicated by the occurrence of double and triple heterozygotes in LQTS and a considerable number of nonpathogenic rare polymorphisms in the involved genes. SQTS is a very rare condition, caused by mutations in five genes (SQTS1-5). The present mutation update is a comprehensive description of all known LQTS- and SQTS-associated mutations.
Hedley
Paula L
PL
Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.
Jørgensen
Poul
P
Schlamowitz
Sarah
S
Wangari
Romilda
R
Moolman-Smook
Johanna
J
Brink
Paul A
PA
Kanters
Jørgen K
JK
Corfield
Valerie A
VA
Christiansen
Michael
M
D054758:A Kinase Anchor Proteins / Q000737:chemistry / Q000235:genetics; D017487:Ankyrins / Q000737:chemistry / Q000235:genetics; D001145:Arrhythmias, Cardiac / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics; D051244:Caveolin 3 / Q000737:chemistry / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D013577:Syndrome
D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; C498994:ANK2 protein, human; D017487:Ankyrins; C417736:CAV3 protein, human; D002135:Calcium-Binding Proteins; D051244:Caveolin 3; D003598:Cytoskeletal Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D009124:Muscle Proteins; C091825:syntrophin alpha1