Prenatal Genetic Diagnosis in Three Fetuses With Left Heart Hypoplasia (LHH) From Three Unrelated Families
Background: Congenital heart defects (CHDs) are the most common birth defects, and left heart hypoplasia (LHH) is a severe form of CHD and responsible for more than 20% cardiac deaths during the first week of life, however, its genetic causes remain largely elusive.Methods: Three families with fetal...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.631374/full |
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| author | Sukun Luo Luyi Chen Weizhong Wei Li Tan Meng Zhang Zhengrong Duan Jiangxia Cao Yan Zhou Aifen Zhou Xuelian He |
| author_facet | Sukun Luo Luyi Chen Weizhong Wei Li Tan Meng Zhang Zhengrong Duan Jiangxia Cao Yan Zhou Aifen Zhou Xuelian He |
| author_sort | Sukun Luo |
| collection | DOAJ |
| description | Background: Congenital heart defects (CHDs) are the most common birth defects, and left heart hypoplasia (LHH) is a severe form of CHD and responsible for more than 20% cardiac deaths during the first week of life, however, its genetic causes remain largely elusive.Methods: Three families with fetal LHH were recruited. Genomic DNA from amniotic fluid or peripheral blood, and trio whole exome sequencing (trio-WES) and copy number variation sequencing (CNV-seq) were performed.Results: All the three couples had no family history, and mid-gestation ultrasound revealed LHH and other variable cardiovascular defects in the fetuses. Trio-WES revealed de novo pathogenic variations in KMT2D (p.Gly3465Aspfs*37) (NM_003482) and WDFY3 (p.Ser117Xfs*) (NM_014991), and CNV-seq identified a deletion of 150 kb encompassing NOTCH1. KMT2D and NOTCH1 previously have been reported to be associated with CHDs, however, WDFY3 is reported for the first time to be possibly related to CHD in human.Conclusion: Our study suggested that genetic component is an important risk factor for the development of LHH, and next generation sequencing is a powerful tool for genetic diagnosis in fetuses with CHDs and genetic counseling, however, more studies and data are need to establish the correlation of fetal phenotypes and genotypes. |
| first_indexed | 2024-12-13T21:50:25Z |
| format | Article |
| id | doaj.art-58187cede91d466484f0b252e12593b6 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-13T21:50:25Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-58187cede91d466484f0b252e12593b62022-12-21T23:30:18ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-04-01810.3389/fcvm.2021.631374631374Prenatal Genetic Diagnosis in Three Fetuses With Left Heart Hypoplasia (LHH) From Three Unrelated FamiliesSukun Luo0Luyi Chen1Weizhong Wei2Li Tan3Meng Zhang4Zhengrong Duan5Jiangxia Cao6Yan Zhou7Aifen Zhou8Xuelian He9Precision Medical Center, Tongji Medical College, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Huazhong University of Science and Technology, Wuhan, ChinaPrenatal Diagnosis Center, Tongji Medical College, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Huazhong University of Science and Technology, Wuhan, ChinaUltrasonic Diagnosis Department, Tongji Medical College, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Huazhong University of Science and Technology, Wuhan, ChinaPrecision Medical Center, Tongji Medical College, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Huazhong University of Science and Technology, Wuhan, ChinaUltrasonic Diagnosis Department, Tongji Medical College, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Huazhong University of Science and Technology, Wuhan, ChinaPrenatal Diagnosis Center, Tongji Medical College, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Huazhong University of Science and Technology, Wuhan, ChinaPrenatal Diagnosis Center, Tongji Medical College, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Huazhong University of Science and Technology, Wuhan, ChinaPrenatal Diagnosis Center, Tongji Medical College, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Huazhong University of Science and Technology, Wuhan, ChinaPrenatal Diagnosis Center, Tongji Medical College, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Huazhong University of Science and Technology, Wuhan, ChinaPrecision Medical Center, Tongji Medical College, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Huazhong University of Science and Technology, Wuhan, ChinaBackground: Congenital heart defects (CHDs) are the most common birth defects, and left heart hypoplasia (LHH) is a severe form of CHD and responsible for more than 20% cardiac deaths during the first week of life, however, its genetic causes remain largely elusive.Methods: Three families with fetal LHH were recruited. Genomic DNA from amniotic fluid or peripheral blood, and trio whole exome sequencing (trio-WES) and copy number variation sequencing (CNV-seq) were performed.Results: All the three couples had no family history, and mid-gestation ultrasound revealed LHH and other variable cardiovascular defects in the fetuses. Trio-WES revealed de novo pathogenic variations in KMT2D (p.Gly3465Aspfs*37) (NM_003482) and WDFY3 (p.Ser117Xfs*) (NM_014991), and CNV-seq identified a deletion of 150 kb encompassing NOTCH1. KMT2D and NOTCH1 previously have been reported to be associated with CHDs, however, WDFY3 is reported for the first time to be possibly related to CHD in human.Conclusion: Our study suggested that genetic component is an important risk factor for the development of LHH, and next generation sequencing is a powerful tool for genetic diagnosis in fetuses with CHDs and genetic counseling, however, more studies and data are need to establish the correlation of fetal phenotypes and genotypes.https://www.frontiersin.org/articles/10.3389/fcvm.2021.631374/fullprenatal diagnosiscongenital heart defectsKMT2DNOTCH1WDFY3 |
| spellingShingle | Sukun Luo Luyi Chen Weizhong Wei Li Tan Meng Zhang Zhengrong Duan Jiangxia Cao Yan Zhou Aifen Zhou Xuelian He Prenatal Genetic Diagnosis in Three Fetuses With Left Heart Hypoplasia (LHH) From Three Unrelated Families Frontiers in Cardiovascular Medicine prenatal diagnosis congenital heart defects KMT2D NOTCH1 WDFY3 |
| title | Prenatal Genetic Diagnosis in Three Fetuses With Left Heart Hypoplasia (LHH) From Three Unrelated Families |
| title_full | Prenatal Genetic Diagnosis in Three Fetuses With Left Heart Hypoplasia (LHH) From Three Unrelated Families |
| title_fullStr | Prenatal Genetic Diagnosis in Three Fetuses With Left Heart Hypoplasia (LHH) From Three Unrelated Families |
| title_full_unstemmed | Prenatal Genetic Diagnosis in Three Fetuses With Left Heart Hypoplasia (LHH) From Three Unrelated Families |
| title_short | Prenatal Genetic Diagnosis in Three Fetuses With Left Heart Hypoplasia (LHH) From Three Unrelated Families |
| title_sort | prenatal genetic diagnosis in three fetuses with left heart hypoplasia lhh from three unrelated families |
| topic | prenatal diagnosis congenital heart defects KMT2D NOTCH1 WDFY3 |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.631374/full |
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