scholarly journals Copy Number Variants and Exome Sequencing Analysis in Six Pairs of Chinese Monozygotic Twins Discordant for Congenital Heart Disease

2017 ◽  
Vol 20 (6) ◽  
pp. 521-532 ◽  
Author(s):  
Yuejuan Xu ◽  
Tingting Li ◽  
Tian Pu ◽  
Ruixue Cao ◽  
Fei Long ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Exome Sequencing ◽  
Copy Number ◽  
Congenital Heart ◽  
Copy Number Variants ◽  
Genetic Mutation ◽  
Sequencing Analysis ◽  
Susceptibility Loci ◽  
Mz Twins

Congenital heart disease (CHD) is one of the most common birth defects. More than 200 susceptibility loci have been identified for CHDs, yet a large part of the genetic risk factors remain unexplained. Monozygotic (MZ) twins are thought to be completely genetically identical; however, discordant phenotypes have been found in MZ twins. Recent studies have demonstrated genetic differences between MZ twins. We aimed to test whether copy number variants (CNVs) and/or genetic mutation differences play a role in the etiology of CHDs by using single nucleotide polymorphism (SNP) genotyping arrays and whole exome sequencing of twin pairs discordant for CHDs. Our goal was to identify mutations present only in the affected twins, which could identify novel candidates for CHD susceptibility loci. We present a comprehensive analysis for the CNVs and genetic mutation results of the selected individuals but detected no consistent differences within the twin pairs. Our study confirms that chromosomal structure or genetic mutation differences do not seem to play a role in the MZ twins discordant for CHD.

scholarly journals Contribution of Global Rare Copy-Number Variants to the Risk of Sporadic Congenital Heart Disease

2012 ◽  
Vol 91 (3) ◽  
pp. 489-501 ◽  
Author(s):  
Rachel Soemedi ◽  
Ian J. Wilson ◽  
Jamie Bentham ◽  
Rebecca Darlay ◽  
Ana Töpf ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Copy Number ◽  
Congenital Heart ◽  
Copy Number Variants

Array CGH as a first-tier test for neonates with congenital heart disease

2013 ◽  
Vol 25 (1) ◽  
pp. 115-122 ◽  
Author(s):  
Kristine K. Bachman ◽  
Stephanie J. DeWard ◽  
Constantinos Chrysostomou ◽  
Ricardo Munoz ◽  
Suneeta Madan-Khetarpal
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Cytogenetic Analysis ◽  
Copy Number ◽  
Congenital Heart ◽  
Clinical Care ◽  
Copy Number Variants ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Array Comparative Genomic Hybridisation

AbstractObjectiveEfficient diagnosis of an underlying genetic aetiology in a patient with congenital heart disease is essential to optimising clinical care. Copy number variants are one aetiology of congenital heart disease; the majority are identifiable by targeted fluorescence in situ hybridisation or array comparative genomic hybridisation, not by classical cytogenetic analysis. This study assessed the utility of array comparative genomic hybridisation as a first-tier diagnostic test for neonates with congenital heart disease.Study designA prospective chart review of neonates with congenital heart disease in the Cardiac Intensive Care Unit at Children’s Hospital of Pittsburgh of UPMC was performed. Patients were tested by array comparative genomic hybridisation and classical cytogenetic analysis simultaneously. Data collected included all chromosome abnormalities detected, physical examination findings, and imaging results. McNemar’s test was used to compare detection of array comparative genomic hybridisation and classical cytogenetic analysis.ResultsOf 45 patients, three (6.7%) had an abnormality detected by classical cytogenetic analysis and an additional 10 (22.2%) had a copy number variant detected by array comparative genomic hybridisation, highlighting an increased detection rate (p=0.008). Several of these copy number variants had unclear clinical significance, requiring additional investigation. The prevalence of dysmorphology and/or comorbidity in this population was 72%. Identification of dysmorphic features was greater when assessed by a geneticist than by providers of different subspecialties.ConclusionsArray comparative genomic hybridisation has significant clinical utility as a first-tier test in this population, but it carries the potential for incidental findings and results of uncertain clinical significance. Collaboration between cardiologists and medical geneticists is essential to providing optimal clinical care.

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