title: A novel custom resequencing array for dilated  cardiomyopathy.
abstract: OBJECTIVE
  Genetic tests for the most commonly mutated genes in dilated cardiomyopathy (DCM) can confirm a clinical diagnosis in the proband and inform family management. Presymptomatic family members can be identified, allowing for targeted clinical monitoring to minimize adverse outcomes. However, the marked locus and allelic heterogeneity associated with DCM have made clinical genetic testing challenging. Novel sequencing platforms have now opened up avenues for more comprehensive diagnostic testing while simultaneously decreasing test cost and turn around time.
  
  
  METHODS
  By using a custom design based on triplicate resequencing and separate genotyping of known disease-causing variants, we developed the DCM CardioChip for efficient analysis of 19 genes previously implicated in causing DCM.
  
  
  RESULTS
  The chip's analytical sensitivity for known and novel substitution variants is 100% and 98%, respectively. In screening 73 previously tested DCM patients who did not carry clinically significant variants in 10 genes, 7 variants of likely clinical significance were identified in the remaining 9 genes included on the chip. Compared with traditional Sanger-based sequencing, test cost and turn around time were reduced by approximately 50%.
  
  
  CONCLUSIONS
  The DCM CardioChip is a highly efficient screening test with a projected clinical sensitivity of 26-29%.
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Center for Personalized Genetic Medicine, Cambridge, Massachusetts 02139, USA.
authors.forename: Rebekah S
authors.initials: RS
authors.lastname: Zimmerman
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cox
authors.forename: Neal K
authors.initials: NK
authors.lastname: Lakdawala
authors.forename: Allison
authors.initials: A
authors.lastname: Cirino
authors.forename: Debora
authors.initials: D
authors.lastname: Mancini-DiNardo
authors.forename: Eugene
authors.initials: E
authors.lastname: Clark
authors.forename: Annette
authors.initials: A
authors.lastname: Leon
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Duffy
authors.forename: Emily
authors.initials: E
authors.lastname: White
authors.forename: Samantha
authors.initials: S
authors.lastname: Baxter
authors.forename: Manal
authors.initials: M
authors.lastname: Alaamery
authors.forename: Lisa
authors.initials: L
authors.lastname: Farwell
authors.forename: Scott
authors.initials: S
authors.lastname: Weiss
authors.forename: Christine E
authors.initials: CE
authors.lastname: Seidman
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Seidman
authors.forename: Carolyn Y
authors.initials: CY
authors.lastname: Ho
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Rehm
authors.forename: Birgit H
authors.initials: BH
authors.lastname: Funke
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000235:genetics*; D005190:Family; D005260:Female; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D011247:Pregnancy
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