Rare De Novo Copy Number Variants in Patients with Congenital Pulmonary Atresia

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 May 16

PMID 24826987

Citations 15

Authors

Li Xie

Jin-Lan Chen

Wei-Zhi Zhang

Shou-Zheng Wang

Tian-Li Zhao

Can Huang

Jian Wang

Jin-Fu Yang

Yi-Feng Yang

Zhi-Ping Tan

Affiliations

Soon will be listed here.

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.

Citing Articles

Copy number variation-associated lncRNAs may contribute to the etiologies of congenital heart disease.

Lu Y, Fang Q, Qi M, Li X, Zhang X, Lin Y Commun Biol. 2023; 6(1):189.

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A Common Polymorphism in the Gene Is a Modulator of Risk of Congenital Heart Disease.

Kuzelicki N, Smid A, Vidmar Golja M, Kek T, Gersak B, Mazic U J Cardiovasc Dev Dis. 2022; 9(6).

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Establishment of a Dihydrofolate Reductase Gene Knock-In Zebrafish Strain to Aid Preliminary Analysis of Congenital Heart Disease Mechanisms.

Gong K, Xie T, Yang Y, Luo Y, Deng Y, Chen K Front Cardiovasc Med. 2022; 8:763851.

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Identification of rare variants in novel candidate genes in pulmonary atresia patients by next generation sequencing.

Shi X, Zhang L, Bai K, Xie H, Shi T, Zhang R Comput Struct Biotechnol J. 2020; 18:381-392.

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Integration of Large-Scale Genomic Data Sources With Evolutionary History Reveals Novel Genetic Loci for Congenital Heart Disease.

Fotiou E, Williams S, Martin-Geary A, Robertson D, Tenin G, Hentges K Circ Genom Precis Med. 2019; 12(10):442-451.

PMID: 31613678 PMC: 6798745. DOI: 10.1161/CIRCGEN.119.002694.

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