title: Phenotypic Variability of ANK2 Mutations in Patients With Inherited Primary Arrhythmia Syndromes.
abstract: Mutations inANK2have been reported to cause various arrhythmia phenotypes. The prevalence ofANK2mutation carriers in inherited primary arrhythmia syndrome (IPAS), however, remains unknown in Japanese. Using a next-generation sequencer, we aimed to identifyANK2mutations in our cohort of IPAS patients, in whom conventional Sanger sequencing failed to identify pathogenic mutations in major causative genes, and to assess the clinical characteristics ofANK2mutation carriers.
  
  
  
  We screened 535 probands with IPAS and analyzed 46 genes including wholeANK2exons using a bench-top NGS (MiSeq, Illumina) or performed whole-exome-sequencing using HiSeq2000 (Illumina). As a result, 12 of 535 probands (2.2%, aged 0-61 years, 5 males) were found to carry 7 different heterozygousANK2mutations.ANK2-W1535R was identified in 5 LQTS patients and 1 symptomatic BrS and was predicted as damaging by multiple prediction software. In total, as to phenotype, there were 8 LQTS, 2 BrS, 1 IVF, and 1 SSS/AF. Surprisingly, 4/8 LQTS patients had the acquired type of LQTS (aLQTS) and suffered torsades de pointes. A total of 7 of 12 patients had documented malignant ventricular tachyarrhythmias.
  
  
  
  VariousANK2mutations are associated with a wide range of phenotypes, including aLQTS, especially with ventricular fibrillation, representing "ankyrin-B" syndrome. (Circ J 2016; 80: 2435-2442).
authors: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science.
authors: Mari
authors: M
authors: Ichikawa
authors: Takeshi
authors: T
authors: Aiba
authors: Seiko
authors: S
authors: Ohno
authors: Daichi
authors: D
authors: Shigemizu
authors: Junichi
authors: J
authors: Ozawa
authors: Keiko
authors: K
authors: Sonoda
authors: Megumi
authors: M
authors: Fukuyama
authors: Hideki
authors: H
authors: Itoh
authors: Yoshihiro
authors: Y
authors: Miyamoto
authors: Tatsuhiko
authors: T
authors: Tsunoda
authors: Takeru
authors: T
authors: Makiyama
authors: Toshihiro
authors: T
authors: Tanaka
authors: Wataru
authors: W
authors: Shimizu
authors: Minoru
authors: M
authors: Horie
mesh_terms: D000328:Adult; D017487:Ankyrins / Q000235:genetics*; D001145:Arrhythmias, Cardiac / Q000453:epidemiology / Q000235:genetics*; D044466:Asian People; D002648:Child; D005091:Exons; D005260:Female; D030342:Genetic Diseases, Inborn / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D013577:Syndrome
chemical_list: C498994:ANK2 protein, human; D017487:Ankyrins