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Rare De Novo Copy Number Variants in Patients with Congenital Pulmonary Atresia
- Source :
- PLoS ONE, PLoS ONE, Vol 9, Iss 5, p e96471 (2014)
- Publication Year :
- 2014
- Publisher :
- Public Library of Science, 2014.
-
Abstract
- BACKGROUND: Ongoing studies using genomic microarrays and next-generation sequencing have demonstrated that the genetic contributions to cardiovascular diseases have been significantly ignored in the past. The aim of this study was to identify rare copy number variants in individuals with congenital pulmonary atresia (PA). METHODS AND RESULTS: Based on the hypothesis that rare structural variants encompassing key genes play an important role in heart development in PA patients, we performed high-resolution genome-wide microarrays for copy number variations (CNVs) in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. CNVs were identified in 17/82 patients (20.7%), and eight of these CNVs (9.8%) are considered potentially pathogenic. Five de novo CNVs occurred at two known congenital heart disease (CHD) loci (16p13.1 and 22q11.2). Two de novo CNVs that may affect folate and vitamin B12 metabolism were identified for the first time. A de novo 1-Mb deletion at 17p13.2 may represent a rare genomic disorder that involves mild intellectual disability and associated facial features. CONCLUSIONS: Rare CNVs contribute to the pathogenesis of PA (9.8%), suggesting that the causes of PA are heterogeneous and pleiotropic. Together with previous data from animal models, our results might help identify a link between CHD and folate-mediated one-carbon metabolism (FOCM). With the accumulation of high-resolution SNP array data, these previously undescribed rare CNVs may help reveal critical gene(s) in CHD and may provide novel insights about CHD pathogenesis.
- Subjects :
- Male
Chromosomes, Human, Pair 22
lcsh:Medicine
Genome-wide association study
Bioinformatics
law.invention
Chromosomal Disorders
law
Morphogenesis
Medicine and Health Sciences
Copy-number variation
lcsh:Science
Child
Polymerase chain reaction
Oligonucleotide Array Sequence Analysis
Ultrasonography
Genetics
Multidisciplinary
Congenital Heart Defects
Vitamin B 12
Child, Preschool
Female
Pulmonary atresia
Research Article
Heart Defects, Congenital
Adolescent
DNA Copy Number Variations
Cardiology
Biology
Folic Acid
medicine
Humans
In patient
Birth Defects
Genetic Association Studies
Clinical Genetics
Chromosome Aberrations
Evolutionary Biology
Population Biology
lcsh:R
Case-control study
Infant, Newborn
Biology and Life Sciences
Infant
Human Genetics
medicine.disease
Human genetics
Folic acid
Genetic Loci
Pulmonary Atresia
Case-Control Studies
Genetics of Disease
Genetic Polymorphism
lcsh:Q
Population Genetics
Chromosomes, Human, Pair 16
Developmental Biology
Chromosomes, Human, Pair 17
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....41da3c50d974b89985aff9da4e8c046c