title: Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy.
abstract: OBJECTIVE
  Genetic testing for hypertrophic cardiomyopathy has been commercially available for almost a decade; however, low mutation detection rate and cost have hindered uptake. This study sought to identify clinical variables that can predict probands with hypertrophic cardiomyopathy in whom a pathogenic mutation will be identified.
  
  
  METHODS
  Probands attending specialized cardiac genetic clinics across Australia over a 10-year period (2002-2011), who met clinical diagnostic criteria for hypertrophic cardiomyopathy and who underwent genetic testing for hypertrophic cardiomyopathy were included. Clinical, family history, and genotype information were collected.
  
  
  RESULTS
  A total of 265 unrelated individuals with hypertrophic cardiomyopathy were included, with 138 (52%) having at least one mutation identified. The mutation detection rate was significantly higher in the probands with hypertrophic cardiomyopathy with an established family history of disease (72 vs. 29%, P < 0.0001), and a positive family history of sudden cardiac death further increased the detection rate (89 vs. 59%, P < 0.0001). Multivariate analysis identified female gender, increased left-ventricular wall thickness, family history of hypertrophic cardiomyopathy, and family history of sudden cardiac death as being associated with greatest chance of identifying a gene mutation. Multiple mutation carriers (n = 16, 6%) were more likely to have suffered an out-of-hospital cardiac arrest or sudden cardiac death (31 vs. 7%, P = 0.012).
  
  
  CONCLUSIONS
  Family history is a key clinical predictor of a positive genetic diagnosis and has direct clinical relevance, particularly in the pretest genetic counseling setting.
authors.affiliation: 1] Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia [2] School of Medicine, University of Sydney, Sydney, Australia.
authors.forename: Jodie
authors.initials: J
authors.lastname: Ingles
authors.forename: Tanya
authors.initials: T
authors.lastname: Sarina
authors.forename: Laura
authors.initials: L
authors.lastname: Yeates
authors.forename: Lauren
authors.initials: L
authors.lastname: Hunt
authors.forename: Ivan
authors.initials: I
authors.lastname: Macciocca
authors.forename: Louise
authors.initials: L
authors.lastname: McCormack
authors.forename: Ingrid
authors.initials: I
authors.lastname: Winship
authors.forename: Julie
authors.initials: J
authors.lastname: McGaughran
authors.forename: John
authors.initials: J
authors.lastname: Atherton
authors.forename: Christopher
authors.initials: C
authors.lastname: Semsarian
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D005260:Female; D005817:Genetic Counseling; D005819:Genetic Markers; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D005819:Genetic Markers