title: Merits and pitfalls of genetic testing in a hypertrophic cardiomyopathy clinic.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM.
  
  
  OBJECTIVE
  To analyze the impact of genetic diagnosis on the clinical management of HCM.
  
  
  METHODS
  Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation.
  
  
  RESULTS
  Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation.
  
  
  CONCLUSIONS
  Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determines the indication for genetic testing and interpretation of the results.
authors.affiliation: Sheba Medical Center, Tel Hashomer, Israel. Michael.arad@sheba.health.gov.il
authors.forename: Michael
authors.initials: M
authors.lastname: Arad
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monserrat
authors.forename: Shiraz
authors.initials: S
authors.lastname: Haron-Khun
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Seidman
authors.forename: Christine E
authors.initials: CE
authors.lastname: Seidman
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
authors.forename: Michael
authors.initials: M
authors.lastname: Glikson
authors.forename: Dov
authors.initials: D
authors.lastname: Freimark
mesh_terms: D017668:Age of Onset; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000523:psychology / Q000628:therapy; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control; D019468:Disease Management; D005192:Family Health; D005260:Female; D006580:Genetic Carrier Screening; D005817:Genetic Counseling / Q000523:psychology / Q000706:statistics & numerical data; D005820:Genetic Testing / Q000379:methods / Q000706:statistics & numerical data; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D009154:Mutation; D010358:Patient Participation / Q000523:psychology; D010375:Pedigree; D018570:Risk Assessment