title: Rapid molecular genetic diagnosis of hypertrophic cardiomyopathy by semiconductor sequencing.
abstract: BACKGROUND
  Rapidly determining the complex genetic basis of Hypertrophic cardiomyopathy (HCM) is vital to better understanding and optimally managing this common polygenetic cardiovascular disease.
  
  
  METHODS
  A rapid custom Ion-amplicon-resequencing assay, covering 30 commonly affected genes of HCM, was developed and validated in 120 unrelated patients with HCM to facilitate genetic diagnosis of this disease. With this HCM-specific panel and only 20 ng of input genomic DNA, physicians can, for the first time, go from blood samples to variants within a single day.
  
  
  RESULTS
  On average, this approach gained 595628 mapped reads per sample, 95.51% reads on target (64.06 kb), 490-fold base coverage depth and 93.24% uniformity of base coverage in CDS regions of the 30 HCM genes. After validation, we detected underlying pathogenic variants in 87% (104 of 120) samples. Tested seven randomly selected HCM genes in eight samples by Sanger sequencing, the sensitivity and false-positive-rate of this HCM panel was 100% and 5%, respectively.
  
  
  CONCLUSIONS
  This Ion amplicon HCM resequencing assay provides a currently most rapid, comprehensive, cost-effective and reliable measure for genetic diagnosis of HCM in routinely obtained samples.
authors.forename: Zongzhe
authors.initials: Z
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Jinzhao
authors.initials: J
authors.lastname: Zhao
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Hu
authors.initials: H
authors.lastname: Ding
authors.affiliation: Departments of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan 430030, China. david37212@hotmail.com.
authors.forename: Dao Wu
authors.initials: DW
authors.lastname: Wang
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D012666:Semiconductors; D017422:Sequence Analysis, DNA / Q000379:methods*