Rapid detection of genetic variants in hypertrophic cardiomyopathy by custom DNA resequencing array in clinical practice.
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease (1/500) and the most common cause of sudden cardiac death in young people. Pathogenic mutation detection of HCM is having a growing impact on the medical management of patients and their families. However, the remarkable genetic and allelic heterogeneity makes molecular analysis by conventional methods very time-consuming, expensive and difficult to realise in a routine diagnostic molecular laboratory.


RESULTS
The authors used their custom DNA resequencing array which interrogates all possible single-nucleotide variants on both strands of all exons (n=160), splice sites and 5'-untranslated region of 12 HCM genes (27 000 nucleotides). The results for 122 unrelated patients with HCM are presented. Thirty-three known or novel potentially pathogenic heterozygous single-nucleotide variants were identified in 38 patients (31%) in genes MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL3 and ACTC1.


CONCLUSIONS
Although next-generation sequencing will replace all large-scale sequencing platforms for inherited cardiac disorders in the near future, this HCM resequencing array is currently the most rapid, cost-effective and reasonably efficient technology for first-tier mutation screening of HCM in clinical practice. Because of its design, the array is also an appropriate tool for initial screening of other inherited forms of cardiomyopathy.
Genetic Medicine, Centre Médical Universitaire, 1 rue Michel-Servet, Geneva, Switzerland. siv.fokstuen@unige.ch
Siv
S
Fokstuen
Analia
A
Munoz
Paola
P
Melacini
Sabino
S
Iliceto
Andreas
A
Perrot
Cemil
C
Ozcelik
Xavier
X
Jeanrenaud
Claudine
C
Rieubland
Martin
M
Farr
Lothar
L
Faber
Ulrich
U
Sigwart
François
F
Mach
René
R
Lerch
Stylianos E
SE
Antonarakis
Jean-Louis
JL
Blouin
D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011364:Professional Practice; D017422:Sequence Analysis, DNA / Q000379:methods*