title: Genetic testing for dilated cardiomyopathy in clinical practice.
abstract: BACKGROUND
  Familial involvement is common in dilated cardiomyopathy (DCM) and >40 genes have been implicated in causing disease. However, the role of genetic testing in clinical practice is not well defined. We examined the experience of clinical genetic testing in a diverse DCM population to characterize the prevalence and predictors of gene mutations.
  
  
  RESULTS
  We studied 264 unrelated adult and pediatric DCM index patients referred to 1 reference lab for clinical genetic testing. Up to 10 genes were analyzed (MYH7, TNNT2, TNNI3, TPM1, MYBPC3, ACTC, LMNA, PLN, TAZ, and LDB3), and 70% of patients were tested for all genes. The mean age was 26.6 ± 21.3 years, and 52% had a family history of DCM. Rigorous criteria were used to classify DNA variants as clinically relevant (mutations), variants of unknown clinical significance (VUS), or presumed benign. Mutations were found in 17.4% of patients, commonly involving MYH7, LMNA, or TNNT2 (78%). An additional 10.6% of patients had VUS. Genetic testing was rarely positive in older patients without a family history of DCM. Conversely in pediatric patients, family history did not increase the sensitivity of genetic testing.
  
  
  CONCLUSIONS
  Using rigorous criteria for classifying DNA variants, mutations were identified in 17% of a diverse group of DCM index patients referred for clinical genetic testing. The low sensitivity of genetic testing in DCM reflects limitations in both current methodology and knowledge of DCM-associated genes. However, if mutations are identified, genetic testing can help guide family management.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Neal K
authors.initials: NK
authors.lastname: Lakdawala
authors.forename: Birgit H
authors.initials: BH
authors.lastname: Funke
authors.forename: Samantha
authors.initials: S
authors.lastname: Baxter
authors.forename: Allison L
authors.initials: AL
authors.lastname: Cirino
authors.forename: Amy E
authors.initials: AE
authors.lastname: Roberts
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.forename: Nicole
authors.initials: N
authors.lastname: Johnson
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Mendelsohn
authors.forename: Chantal
authors.initials: C
authors.lastname: Morel
authors.forename: Melanie
authors.initials: M
authors.lastname: Care
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Carolyn
authors.initials: C
authors.lastname: Jones
authors.forename: Apostolos
authors.initials: A
authors.lastname: Psychogios
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Duffy
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Rehm
authors.forename: Emily
authors.initials: E
authors.lastname: White
authors.forename: J G
authors.initials: JG
authors.lastname: Seidman
authors.forename: Christine E
authors.initials: CE
authors.lastname: Seidman
authors.forename: Carolyn Y
authors.initials: CY
authors.lastname: Ho
mesh_terms: D000293:Adolescent; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D012518:Sarcomeres / Q000235:genetics; D055815:Young Adult; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C