Rare Variants in Novel Candidate Genes Associated With Nonsyndromic Patent Ductus Arteriosus Identified With Whole-Exome Sequencing
Background: Patent ductus arteriosus (PDA) is one of the most common congenital heart defects causing pulmonary hypertension, infective endocarditis, and even death. The important role of genetics in determining spontaneous ductal closure has been well-established. However, as many of the identified...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.921925/full |
| _version_ | 1811244501575925760 |
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| author | Ying Gao Dan Wu Bo Chen Yinghui Chen Qi Zhang Pengjun Zhao |
| author_facet | Ying Gao Dan Wu Bo Chen Yinghui Chen Qi Zhang Pengjun Zhao |
| author_sort | Ying Gao |
| collection | DOAJ |
| description | Background: Patent ductus arteriosus (PDA) is one of the most common congenital heart defects causing pulmonary hypertension, infective endocarditis, and even death. The important role of genetics in determining spontaneous ductal closure has been well-established. However, as many of the identified variants are rare, thorough identification of the associated genetic factors is necessary to further explore the genetic etiology of PDA.Methods: We performed whole-exome sequencing (WES) on 39 isolated nonsyndromic PDA patients and 100 healthy controls. Rare variants and novel genes were identified through bioinformatic filtering strategies. The expression patterns of candidate genes were explored in human embryo heart samples.Results: Eighteen rare damaging variants of six novel PDA-associated genes (SOX8, NES, CDH2, ANK3, EIF4G1, and HIPK1) were newly identified, which were highly expressed in human embryo hearts.Conclusions: WES is an efficient diagnostic tool for exploring the genetic pathogenesis of PDA. These findings contribute new insights into the molecular basis of PDA and may inform further studies on genetic risk factors for congenital heart defects. |
| first_indexed | 2024-04-12T14:26:10Z |
| format | Article |
| id | doaj.art-529395808ce84cf69f2cc5f76ea8f302 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T14:26:10Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-529395808ce84cf69f2cc5f76ea8f3022022-12-22T03:29:25ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-06-011310.3389/fgene.2022.921925921925Rare Variants in Novel Candidate Genes Associated With Nonsyndromic Patent Ductus Arteriosus Identified With Whole-Exome SequencingYing Gao0Dan Wu1Bo Chen2Yinghui Chen3Qi Zhang4Pengjun Zhao5Department of Pediatric, Shidong Hospital, Shanghai, ChinaDepartment of Pediatric, Shidong Hospital, Shanghai, ChinaDepartment of Cardiothoracic Surgery, School of Medicine, Heart Center, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaBackground: Patent ductus arteriosus (PDA) is one of the most common congenital heart defects causing pulmonary hypertension, infective endocarditis, and even death. The important role of genetics in determining spontaneous ductal closure has been well-established. However, as many of the identified variants are rare, thorough identification of the associated genetic factors is necessary to further explore the genetic etiology of PDA.Methods: We performed whole-exome sequencing (WES) on 39 isolated nonsyndromic PDA patients and 100 healthy controls. Rare variants and novel genes were identified through bioinformatic filtering strategies. The expression patterns of candidate genes were explored in human embryo heart samples.Results: Eighteen rare damaging variants of six novel PDA-associated genes (SOX8, NES, CDH2, ANK3, EIF4G1, and HIPK1) were newly identified, which were highly expressed in human embryo hearts.Conclusions: WES is an efficient diagnostic tool for exploring the genetic pathogenesis of PDA. These findings contribute new insights into the molecular basis of PDA and may inform further studies on genetic risk factors for congenital heart defects.https://www.frontiersin.org/articles/10.3389/fgene.2022.921925/fullcongenital heart defectspatent ductus arteriosuswhole-exome sequencingrare variantssingle-nucleotide polymorphism |
| spellingShingle | Ying Gao Dan Wu Bo Chen Yinghui Chen Qi Zhang Pengjun Zhao Rare Variants in Novel Candidate Genes Associated With Nonsyndromic Patent Ductus Arteriosus Identified With Whole-Exome Sequencing Frontiers in Genetics congenital heart defects patent ductus arteriosus whole-exome sequencing rare variants single-nucleotide polymorphism |
| title | Rare Variants in Novel Candidate Genes Associated With Nonsyndromic Patent Ductus Arteriosus Identified With Whole-Exome Sequencing |
| title_full | Rare Variants in Novel Candidate Genes Associated With Nonsyndromic Patent Ductus Arteriosus Identified With Whole-Exome Sequencing |
| title_fullStr | Rare Variants in Novel Candidate Genes Associated With Nonsyndromic Patent Ductus Arteriosus Identified With Whole-Exome Sequencing |
| title_full_unstemmed | Rare Variants in Novel Candidate Genes Associated With Nonsyndromic Patent Ductus Arteriosus Identified With Whole-Exome Sequencing |
| title_short | Rare Variants in Novel Candidate Genes Associated With Nonsyndromic Patent Ductus Arteriosus Identified With Whole-Exome Sequencing |
| title_sort | rare variants in novel candidate genes associated with nonsyndromic patent ductus arteriosus identified with whole exome sequencing |
| topic | congenital heart defects patent ductus arteriosus whole-exome sequencing rare variants single-nucleotide polymorphism |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.921925/full |
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