Identifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES)
Abstract Background Whole-exome sequencing (WES) has become an invaluable tool for genetic diagnosis in paediatrics. However, it has not been widely adopted in the prenatal setting. This study evaluated the use of WES in prenatal genetic diagnosis in fetuses with structural congenital anomalies (SCA...
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BMC
2018-10-01
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| Series: | BMC Medical Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12920-018-0409-z |
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| author | Gordon K C Leung Christopher C Y Mak Jasmine L F Fung Wilfred H S Wong Mandy H Y Tsang Mullin H C Yu Steven L C Pei K S Yeung Gary T K Mok C P Lee Amelia P W Hui Mary H Y Tang Kelvin Y K Chan Anthony P Y Liu Wanling Yang P C Sham Anita S Y Kan Brian H Y Chung |
| author_facet | Gordon K C Leung Christopher C Y Mak Jasmine L F Fung Wilfred H S Wong Mandy H Y Tsang Mullin H C Yu Steven L C Pei K S Yeung Gary T K Mok C P Lee Amelia P W Hui Mary H Y Tang Kelvin Y K Chan Anthony P Y Liu Wanling Yang P C Sham Anita S Y Kan Brian H Y Chung |
| author_sort | Gordon K C Leung |
| collection | DOAJ |
| description | Abstract Background Whole-exome sequencing (WES) has become an invaluable tool for genetic diagnosis in paediatrics. However, it has not been widely adopted in the prenatal setting. This study evaluated the use of WES in prenatal genetic diagnosis in fetuses with structural congenital anomalies (SCAs) detected on prenatal ultrasound. Method Thirty-three families with fetal SCAs on prenatal ultrasonography and normal chromosomal microarray results were recruited. Genomic DNA was extracted from various fetal samples including amniotic fluid, chorionic villi, and placental tissue. Parental DNA was extracted from peripheral blood when available. We used WES to sequence the coding regions of parental-fetal trios and to identify the causal variants based on the ultrasonographic features of the fetus. Results Pathogenic mutations were identified in three families (n = 3/33, 9.1%), including mutations in DNAH11, RAF1 and CHD7, which were associated with primary ciliary dyskinesia, Noonan syndrome, and CHARGE syndrome, respectively. In addition, variants of unknown significance (VUSs) were detected in six families (18.2%), in which genetic changes only partly explained prenatal features. Conclusion WES identified pathogenic mutations in 9.1% of fetuses with SCAs and normal chromosomal microarray results. Databases for fetal genotype-phenotype correlations and standardized guidelines for variant interpretation in prenatal diagnosis need to be established to facilitate the use of WES for routine testing in prenatal diagnosis. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-17T22:28:15Z |
| publishDate | 2018-10-01 |
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| series | BMC Medical Genomics |
| spelling | doaj.art-282d5793434f48b0ae2433ea3829b9192022-12-21T21:30:17ZengBMCBMC Medical Genomics1755-87942018-10-0111111010.1186/s12920-018-0409-zIdentifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES)Gordon K C Leung0Christopher C Y Mak1Jasmine L F Fung2Wilfred H S Wong3Mandy H Y Tsang4Mullin H C Yu5Steven L C Pei6K S Yeung7Gary T K Mok8C P Lee9Amelia P W Hui10Mary H Y Tang11Kelvin Y K Chan12Anthony P Y Liu13Wanling Yang14P C Sham15Anita S Y Kan16Brian H Y Chung17Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong KongDepartment of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong KongDepartment of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong KongDepartment of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong KongDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Psychiatry, LKS Faculty of Medicine, The University of Hong KongDepartment of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong KongDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongAbstract Background Whole-exome sequencing (WES) has become an invaluable tool for genetic diagnosis in paediatrics. However, it has not been widely adopted in the prenatal setting. This study evaluated the use of WES in prenatal genetic diagnosis in fetuses with structural congenital anomalies (SCAs) detected on prenatal ultrasound. Method Thirty-three families with fetal SCAs on prenatal ultrasonography and normal chromosomal microarray results were recruited. Genomic DNA was extracted from various fetal samples including amniotic fluid, chorionic villi, and placental tissue. Parental DNA was extracted from peripheral blood when available. We used WES to sequence the coding regions of parental-fetal trios and to identify the causal variants based on the ultrasonographic features of the fetus. Results Pathogenic mutations were identified in three families (n = 3/33, 9.1%), including mutations in DNAH11, RAF1 and CHD7, which were associated with primary ciliary dyskinesia, Noonan syndrome, and CHARGE syndrome, respectively. In addition, variants of unknown significance (VUSs) were detected in six families (18.2%), in which genetic changes only partly explained prenatal features. Conclusion WES identified pathogenic mutations in 9.1% of fetuses with SCAs and normal chromosomal microarray results. Databases for fetal genotype-phenotype correlations and standardized guidelines for variant interpretation in prenatal diagnosis need to be established to facilitate the use of WES for routine testing in prenatal diagnosis.http://link.springer.com/article/10.1186/s12920-018-0409-zPrenatal exomeVariants of unknown clinical significancePhenotyping |
| spellingShingle | Gordon K C Leung Christopher C Y Mak Jasmine L F Fung Wilfred H S Wong Mandy H Y Tsang Mullin H C Yu Steven L C Pei K S Yeung Gary T K Mok C P Lee Amelia P W Hui Mary H Y Tang Kelvin Y K Chan Anthony P Y Liu Wanling Yang P C Sham Anita S Y Kan Brian H Y Chung Identifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES) BMC Medical Genomics Prenatal exome Variants of unknown clinical significance Phenotyping |
| title | Identifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES) |
| title_full | Identifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES) |
| title_fullStr | Identifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES) |
| title_full_unstemmed | Identifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES) |
| title_short | Identifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES) |
| title_sort | identifying the genetic causes for prenatally diagnosed structural congenital anomalies scas by whole exome sequencing wes |
| topic | Prenatal exome Variants of unknown clinical significance Phenotyping |
| url | http://link.springer.com/article/10.1186/s12920-018-0409-z |
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