A novel custom resequencing array for dilated  cardiomyopathy.
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%.
Zimmerman
Rebekah S
RS
Laboratory for Molecular Medicine, Partners HealthCare Center for Personalized Genetic Medicine, Cambridge, Massachusetts 02139, USA.
Cox
Stephanie
S
Lakdawala
Neal K
NK
Cirino
Allison
A
Mancini-DiNardo
Debora
D
Clark
Eugene
E
Leon
Annette
A
Duffy
Elizabeth
E
White
Emily
E
Baxter
Samantha
S
Alaamery
Manal
M
Farwell
Lisa
L
Weiss
Scott
S
Seidman
Christine E
CE
Seidman
Jonathan G
JG
Ho
Carolyn Y
CY
Rehm
Heidi L
HL
Funke
Birgit H
BH
D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000235:genetics*; D005190:Family; D005260:Female; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D011247:Pregnancy
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