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Microdeletions and microduplications in patients with congenital heart disease
and multiple congenital anomalies
#MMPMID22010865
Goldmuntz E
; Paluru P
; Glessner J
; Hakonarson H
; Biegel JA
; White PS
; Gai X
; Shaikh TH
Congenit Heart Dis
2011[Nov]; 6
(6
): 592-602
PMID22010865
show ga
OBJECTIVE: Multiple genetic syndromes are caused by recurrent chromosomal
microdeletions or microduplications. The increasing use of high-resolution
microarrays in clinical analysis has allowed the identification of previously
undetectable submicroscopic copy number variants (CNVs) associated with genetic
disorders. We hypothesized that patients with congenital heart disease and
additional dysmorphic features or other anomalies would be likely to harbor
previously undetected CNVs, which might identify new disease loci or
disease-related genes for various cardiac defects. DESIGN: Copy number analysis
with single nucleotide polymorphism-based, oligonucleotide microarrays was
performed on 58 patients with congenital heart disease and other dysmorphic
features and/or other anomalies. The observed CNVs were validated using
independent techniques and validated CNVs were further analyzed using
computational algorithms and comparison with available control CNV datasets in
order to assess their pathogenic potential. RESULTS: Potentially pathogenic CNVs
were detected in twelve of 58 patients (20.7%), ranging in size from 240?Kb to
9.6?Mb. These CNVs contained between 1 and 55 genes, including NRP1, NTRK3,
MESP1, ADAM19, and HAND1, all of which are known to participate in cardiac
development. CONCLUSIONS: Genome-wide analysis in patients with congenital heart
disease and additional phenotypes has identified potentially pathogenic CNVs
affecting genes involved in cardiac development. The identified variant loci and
the genes within them warrant further evaluation in similarly syndromic and
nonsyndromic cardiac cohorts.
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