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Article: Identifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES)

TitleIdentifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES)
Authors
KeywordsPrenatal exome
Variants of unknown clinical significance
Phenotyping
Issue Date2018
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcmedgenomics/
Citation
BMC Medical Genomics, 2018, v. 11 n. 1, article no. 93, p. 1-10 How to Cite?
AbstractBackground: 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.
Persistent Identifierhttp://hdl.handle.net/10722/266090
ISSN
2017 Impact Factor: 3.317
2015 SCImago Journal Rankings: 1.710
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLeung, KC-
dc.contributor.authorMak, CCY-
dc.contributor.authorFung, LF-
dc.contributor.authorWong, WHS-
dc.contributor.authorTsang, HY-
dc.contributor.authorYu, HC-
dc.contributor.authorPei, LCS-
dc.contributor.authorYeung, KS-
dc.contributor.authorMok, TKG-
dc.contributor.authorLee, CP-
dc.contributor.authorHui, PW-
dc.contributor.authorTang, MHY-
dc.contributor.authorChan, YK-
dc.contributor.authorLiu, APY-
dc.contributor.authorYang, W-
dc.contributor.authorSham, PC-
dc.contributor.authorKan, SYA-
dc.contributor.authorChung, BHY-
dc.date.accessioned2018-12-17T02:16:45Z-
dc.date.available2018-12-17T02:16:45Z-
dc.date.issued2018-
dc.identifier.citationBMC Medical Genomics, 2018, v. 11 n. 1, article no. 93, p. 1-10-
dc.identifier.issn1755-8794-
dc.identifier.urihttp://hdl.handle.net/10722/266090-
dc.description.abstractBackground: 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.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcmedgenomics/-
dc.relation.ispartofBMC Medical Genomics-
dc.rightsBMC Medical Genomics. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectPrenatal exome-
dc.subjectVariants of unknown clinical significance-
dc.subjectPhenotyping-
dc.titleIdentifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES)-
dc.typeArticle-
dc.identifier.emailLeung, KC: gleungkc@hku.hk-
dc.identifier.emailFung, LF: jasflf@connect.hku.hk-
dc.identifier.emailWong, WHS: whswong@hku.hk-
dc.identifier.emailPei, LCS: slcpei@hku.hk-
dc.identifier.emailYeung, KS: ksyyeung@hku.hk-
dc.identifier.emailLee, CP: chinpeng@hkucc.hku.hk-
dc.identifier.emailHui, PW: apwhui@hkucc.hku.hk-
dc.identifier.emailTang, MHY: mhytang@hkucc.hku.hk-
dc.identifier.emailChan, YK: ykchanc@hku.hk-
dc.identifier.emailLiu, APY: apyliu@hku.hk-
dc.identifier.emailYang, W: yangwl@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailKan, SYA: kansya@hkucc.hku.hk-
dc.identifier.emailChung, BHY: bhychung@hku.hk-
dc.identifier.authorityLee, CP=rp01862-
dc.identifier.authorityTang, MHY=rp01701-
dc.identifier.authorityChan, YK=rp00453-
dc.identifier.authorityLiu, APY=rp01357-
dc.identifier.authorityYang, W=rp00524-
dc.identifier.authoritySham, PC=rp00459-
dc.identifier.authorityChung, BHY=rp00473-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s12920-018-0409-z-
dc.identifier.pmid30359267-
dc.identifier.pmcidPMC6202811-
dc.identifier.scopuseid_2-s2.0-85055616800-
dc.identifier.hkuros296434-
dc.identifier.volume11-
dc.identifier.issue1-
dc.identifier.spagearticle no. 93, p. 1-
dc.identifier.epagearticle no. 93, p. 10-
dc.identifier.isiWOS:000448649400001-
dc.publisher.placeUnited Kingdom-

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