Loading…
A single center experience of prenatal parent‐fetus trio exome sequencing for pregnancies with congenital anomalies
Objectives To examine the diagnostic yield of trio exome sequencing in fetuses with multiple structural defects with no pathogenic findings in cytogenetic and microarray analyses. Methods We recruited 51 fetuses with two or more defects, non‐immune fetal hydrops or fetal akinesia deformation syndrom...
Saved in:
| Published in: | Prenatal diagnosis 2022-06, Vol.42 (7), p.901-910 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c3780-fb4c2b305255d76fee170f1ab6c2c5bde3b2f2a4a595b214946ce7bff530ca423 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c3780-fb4c2b305255d76fee170f1ab6c2c5bde3b2f2a4a595b214946ce7bff530ca423 |
| container_end_page | 910 |
| container_issue | 7 |
| container_start_page | 901 |
| container_title | Prenatal diagnosis |
| container_volume | 42 |
| creator | Dufke, Andreas Hoopmann, Markus Waldmüller, Stephan Prodan, Natalia Carmen Beck‐Wödl, Stefanie Grasshoff, Ute Heinrich, Tilman Riess, Angelika Kehrer, Martin Falb, Ruth J. Liebmann, Alexandra Roggia, Cristiana Stampfer, Miriam Schadeck, Malou Müller, Amelie J. Grimmel, Mona Stöbe, Petra Gauck, Darja Buchert‐Lo, Rebecca Baumann, Sarah Schäferhoff, Karin Bertrand, Miriam Menden, Benita Sturm, Marc Schütz, Leon Riess, Olaf Ossowski, Stephan Haack, Tobias B. Kagan, Karl Oliver |
| description | Objectives
To examine the diagnostic yield of trio exome sequencing in fetuses with multiple structural defects with no pathogenic findings in cytogenetic and microarray analyses.
Methods
We recruited 51 fetuses with two or more defects, non‐immune fetal hydrops or fetal akinesia deformation syndrome|or fetal akinesia deformation sequence (FADS). Trio exome sequencing was performed on DNA from chorionic villi samples and parental blood. Detection of genomic variation and prioritization of clinically relevant variants was performed according to in‐house standard operating procedures.
Results
Median maternal and gestational age was 32.0 years and 21.0 weeks, respectively. Forty‐three (84.3%) fetuses had two or more affected organ systems. The remaining fetuses had isolated fetal hydrops or FADS. In total, the exome analysis established the genetic cause for the clinical abnormalities in 22 (43.1%, 95% CI 29.4%–57.8%) pregnancies.
Conclusions
In fetuses with multiple defects, hydrops or FADS and normal standard genetic results, trio exome sequencing has the potential to identify genetic anomalies in more than 40% of cases.
Key points
What's already known about this topic?
Genome‐wide sequencing for unspecific heterogeneous syndromic and non‐syndromic congenital conditions increases the diagnostic yield compared with standard genetic testing in both the pre‐ and postnatal settings. The diagnostic yield prenatally varies depending on selection criteria and number of anomalies present.
What does this study add?
Trio exome sequencing should be considered for fetuses with normal cytogenetic and micro‐array analysis and two or more organ defects, fetal hydrops or fetal akinesia syndromes. Selection of cases for exome sequencing should be based on expert prenatal imaging. |
| doi_str_mv | 10.1002/pd.6170 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2665112907</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2676883374</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3780-fb4c2b305255d76fee170f1ab6c2c5bde3b2f2a4a595b214946ce7bff530ca423</originalsourceid><addsrcrecordid>eNp10ctKxDAUBuAgijOO4htIwIWCjObSNO1y8A6CLnRd0vRkrLRJTVpGdz6Cz-iTmHHUheAqJ-TLz0kOQruUHFNC2ElXHadUkjU0piSXU8IYX0djQmPNM0FHaCuEpwgzlstNNOJCyCTPyRgNMxxqO28Aa7A9eAwvHfgarAbsDO48WNWrBncqVv3H27uBfgi497WL1LWAAzwPkccQbJxf3phbFfcQ8KLuH7F2dg62XoYo61rVxJNttGFUE2Dne52gh4vz-9Or6c3t5fXp7GaquczI1JSJZiUngglRydQAxDcaqspUMy3KCnjJDFOJErkoGU3yJNUgS2MEJ1oljE_Q4Sq38y52GfqirYOGplEW3BAKlqaCUpYTGen-H_rkBm9jd1HJNMs4l0lUByulvQvBgyk6X7fKvxaUFMtJFF1VLCcR5d533lC2UP26n6-P4GgFFnUDr__lFHdnX3GfE_aTjA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2676883374</pqid></control><display><type>article</type><title>A single center experience of prenatal parent‐fetus trio exome sequencing for pregnancies with congenital anomalies</title><source>Wiley</source><creator>Dufke, Andreas ; Hoopmann, Markus ; Waldmüller, Stephan ; Prodan, Natalia Carmen ; Beck‐Wödl, Stefanie ; Grasshoff, Ute ; Heinrich, Tilman ; Riess, Angelika ; Kehrer, Martin ; Falb, Ruth J. ; Liebmann, Alexandra ; Roggia, Cristiana ; Stampfer, Miriam ; Schadeck, Malou ; Müller, Amelie J. ; Grimmel, Mona ; Stöbe, Petra ; Gauck, Darja ; Buchert‐Lo, Rebecca ; Baumann, Sarah ; Schäferhoff, Karin ; Bertrand, Miriam ; Menden, Benita ; Sturm, Marc ; Schütz, Leon ; Riess, Olaf ; Ossowski, Stephan ; Haack, Tobias B. ; Kagan, Karl Oliver</creator><creatorcontrib>Dufke, Andreas ; Hoopmann, Markus ; Waldmüller, Stephan ; Prodan, Natalia Carmen ; Beck‐Wödl, Stefanie ; Grasshoff, Ute ; Heinrich, Tilman ; Riess, Angelika ; Kehrer, Martin ; Falb, Ruth J. ; Liebmann, Alexandra ; Roggia, Cristiana ; Stampfer, Miriam ; Schadeck, Malou ; Müller, Amelie J. ; Grimmel, Mona ; Stöbe, Petra ; Gauck, Darja ; Buchert‐Lo, Rebecca ; Baumann, Sarah ; Schäferhoff, Karin ; Bertrand, Miriam ; Menden, Benita ; Sturm, Marc ; Schütz, Leon ; Riess, Olaf ; Ossowski, Stephan ; Haack, Tobias B. ; Kagan, Karl Oliver</creatorcontrib><description>Objectives
To examine the diagnostic yield of trio exome sequencing in fetuses with multiple structural defects with no pathogenic findings in cytogenetic and microarray analyses.
Methods
We recruited 51 fetuses with two or more defects, non‐immune fetal hydrops or fetal akinesia deformation syndrome|or fetal akinesia deformation sequence (FADS). Trio exome sequencing was performed on DNA from chorionic villi samples and parental blood. Detection of genomic variation and prioritization of clinically relevant variants was performed according to in‐house standard operating procedures.
Results
Median maternal and gestational age was 32.0 years and 21.0 weeks, respectively. Forty‐three (84.3%) fetuses had two or more affected organ systems. The remaining fetuses had isolated fetal hydrops or FADS. In total, the exome analysis established the genetic cause for the clinical abnormalities in 22 (43.1%, 95% CI 29.4%–57.8%) pregnancies.
Conclusions
In fetuses with multiple defects, hydrops or FADS and normal standard genetic results, trio exome sequencing has the potential to identify genetic anomalies in more than 40% of cases.
Key points
What's already known about this topic?
Genome‐wide sequencing for unspecific heterogeneous syndromic and non‐syndromic congenital conditions increases the diagnostic yield compared with standard genetic testing in both the pre‐ and postnatal settings. The diagnostic yield prenatally varies depending on selection criteria and number of anomalies present.
What does this study add?
Trio exome sequencing should be considered for fetuses with normal cytogenetic and micro‐array analysis and two or more organ defects, fetal hydrops or fetal akinesia syndromes. Selection of cases for exome sequencing should be based on expert prenatal imaging.</description><identifier>ISSN: 0197-3851</identifier><identifier>EISSN: 1097-0223</identifier><identifier>DOI: 10.1002/pd.6170</identifier><identifier>PMID: 35574990</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Abnormalities ; Akinesia ; Congenital anomalies ; Congenital defects ; Cytogenetics ; Defects ; Deformation ; DNA microarrays ; DNA sequencing ; Edema ; Fetuses ; Genetic analysis ; Gestational age ; Nucleotide sequence ; Pregnancy ; Zebrafish</subject><ispartof>Prenatal diagnosis, 2022-06, Vol.42 (7), p.901-910</ispartof><rights>2022 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.</rights><rights>2022. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3780-fb4c2b305255d76fee170f1ab6c2c5bde3b2f2a4a595b214946ce7bff530ca423</citedby><cites>FETCH-LOGICAL-c3780-fb4c2b305255d76fee170f1ab6c2c5bde3b2f2a4a595b214946ce7bff530ca423</cites><orcidid>0000-0002-5616-5010</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpd.6170$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpd.6170$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35574990$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dufke, Andreas</creatorcontrib><creatorcontrib>Hoopmann, Markus</creatorcontrib><creatorcontrib>Waldmüller, Stephan</creatorcontrib><creatorcontrib>Prodan, Natalia Carmen</creatorcontrib><creatorcontrib>Beck‐Wödl, Stefanie</creatorcontrib><creatorcontrib>Grasshoff, Ute</creatorcontrib><creatorcontrib>Heinrich, Tilman</creatorcontrib><creatorcontrib>Riess, Angelika</creatorcontrib><creatorcontrib>Kehrer, Martin</creatorcontrib><creatorcontrib>Falb, Ruth J.</creatorcontrib><creatorcontrib>Liebmann, Alexandra</creatorcontrib><creatorcontrib>Roggia, Cristiana</creatorcontrib><creatorcontrib>Stampfer, Miriam</creatorcontrib><creatorcontrib>Schadeck, Malou</creatorcontrib><creatorcontrib>Müller, Amelie J.</creatorcontrib><creatorcontrib>Grimmel, Mona</creatorcontrib><creatorcontrib>Stöbe, Petra</creatorcontrib><creatorcontrib>Gauck, Darja</creatorcontrib><creatorcontrib>Buchert‐Lo, Rebecca</creatorcontrib><creatorcontrib>Baumann, Sarah</creatorcontrib><creatorcontrib>Schäferhoff, Karin</creatorcontrib><creatorcontrib>Bertrand, Miriam</creatorcontrib><creatorcontrib>Menden, Benita</creatorcontrib><creatorcontrib>Sturm, Marc</creatorcontrib><creatorcontrib>Schütz, Leon</creatorcontrib><creatorcontrib>Riess, Olaf</creatorcontrib><creatorcontrib>Ossowski, Stephan</creatorcontrib><creatorcontrib>Haack, Tobias B.</creatorcontrib><creatorcontrib>Kagan, Karl Oliver</creatorcontrib><title>A single center experience of prenatal parent‐fetus trio exome sequencing for pregnancies with congenital anomalies</title><title>Prenatal diagnosis</title><addtitle>Prenat Diagn</addtitle><description>Objectives
To examine the diagnostic yield of trio exome sequencing in fetuses with multiple structural defects with no pathogenic findings in cytogenetic and microarray analyses.
Methods
We recruited 51 fetuses with two or more defects, non‐immune fetal hydrops or fetal akinesia deformation syndrome|or fetal akinesia deformation sequence (FADS). Trio exome sequencing was performed on DNA from chorionic villi samples and parental blood. Detection of genomic variation and prioritization of clinically relevant variants was performed according to in‐house standard operating procedures.
Results
Median maternal and gestational age was 32.0 years and 21.0 weeks, respectively. Forty‐three (84.3%) fetuses had two or more affected organ systems. The remaining fetuses had isolated fetal hydrops or FADS. In total, the exome analysis established the genetic cause for the clinical abnormalities in 22 (43.1%, 95% CI 29.4%–57.8%) pregnancies.
Conclusions
In fetuses with multiple defects, hydrops or FADS and normal standard genetic results, trio exome sequencing has the potential to identify genetic anomalies in more than 40% of cases.
Key points
What's already known about this topic?
Genome‐wide sequencing for unspecific heterogeneous syndromic and non‐syndromic congenital conditions increases the diagnostic yield compared with standard genetic testing in both the pre‐ and postnatal settings. The diagnostic yield prenatally varies depending on selection criteria and number of anomalies present.
What does this study add?
Trio exome sequencing should be considered for fetuses with normal cytogenetic and micro‐array analysis and two or more organ defects, fetal hydrops or fetal akinesia syndromes. Selection of cases for exome sequencing should be based on expert prenatal imaging.</description><subject>Abnormalities</subject><subject>Akinesia</subject><subject>Congenital anomalies</subject><subject>Congenital defects</subject><subject>Cytogenetics</subject><subject>Defects</subject><subject>Deformation</subject><subject>DNA microarrays</subject><subject>DNA sequencing</subject><subject>Edema</subject><subject>Fetuses</subject><subject>Genetic analysis</subject><subject>Gestational age</subject><subject>Nucleotide sequence</subject><subject>Pregnancy</subject><subject>Zebrafish</subject><issn>0197-3851</issn><issn>1097-0223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp10ctKxDAUBuAgijOO4htIwIWCjObSNO1y8A6CLnRd0vRkrLRJTVpGdz6Cz-iTmHHUheAqJ-TLz0kOQruUHFNC2ElXHadUkjU0piSXU8IYX0djQmPNM0FHaCuEpwgzlstNNOJCyCTPyRgNMxxqO28Aa7A9eAwvHfgarAbsDO48WNWrBncqVv3H27uBfgi497WL1LWAAzwPkccQbJxf3phbFfcQ8KLuH7F2dg62XoYo61rVxJNttGFUE2Dne52gh4vz-9Or6c3t5fXp7GaquczI1JSJZiUngglRydQAxDcaqspUMy3KCnjJDFOJErkoGU3yJNUgS2MEJ1oljE_Q4Sq38y52GfqirYOGplEW3BAKlqaCUpYTGen-H_rkBm9jd1HJNMs4l0lUByulvQvBgyk6X7fKvxaUFMtJFF1VLCcR5d533lC2UP26n6-P4GgFFnUDr__lFHdnX3GfE_aTjA</recordid><startdate>202206</startdate><enddate>202206</enddate><creator>Dufke, Andreas</creator><creator>Hoopmann, Markus</creator><creator>Waldmüller, Stephan</creator><creator>Prodan, Natalia Carmen</creator><creator>Beck‐Wödl, Stefanie</creator><creator>Grasshoff, Ute</creator><creator>Heinrich, Tilman</creator><creator>Riess, Angelika</creator><creator>Kehrer, Martin</creator><creator>Falb, Ruth J.</creator><creator>Liebmann, Alexandra</creator><creator>Roggia, Cristiana</creator><creator>Stampfer, Miriam</creator><creator>Schadeck, Malou</creator><creator>Müller, Amelie J.</creator><creator>Grimmel, Mona</creator><creator>Stöbe, Petra</creator><creator>Gauck, Darja</creator><creator>Buchert‐Lo, Rebecca</creator><creator>Baumann, Sarah</creator><creator>Schäferhoff, Karin</creator><creator>Bertrand, Miriam</creator><creator>Menden, Benita</creator><creator>Sturm, Marc</creator><creator>Schütz, Leon</creator><creator>Riess, Olaf</creator><creator>Ossowski, Stephan</creator><creator>Haack, Tobias B.</creator><creator>Kagan, Karl Oliver</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5616-5010</orcidid></search><sort><creationdate>202206</creationdate><title>A single center experience of prenatal parent‐fetus trio exome sequencing for pregnancies with congenital anomalies</title><author>Dufke, Andreas ; Hoopmann, Markus ; Waldmüller, Stephan ; Prodan, Natalia Carmen ; Beck‐Wödl, Stefanie ; Grasshoff, Ute ; Heinrich, Tilman ; Riess, Angelika ; Kehrer, Martin ; Falb, Ruth J. ; Liebmann, Alexandra ; Roggia, Cristiana ; Stampfer, Miriam ; Schadeck, Malou ; Müller, Amelie J. ; Grimmel, Mona ; Stöbe, Petra ; Gauck, Darja ; Buchert‐Lo, Rebecca ; Baumann, Sarah ; Schäferhoff, Karin ; Bertrand, Miriam ; Menden, Benita ; Sturm, Marc ; Schütz, Leon ; Riess, Olaf ; Ossowski, Stephan ; Haack, Tobias B. ; Kagan, Karl Oliver</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3780-fb4c2b305255d76fee170f1ab6c2c5bde3b2f2a4a595b214946ce7bff530ca423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Abnormalities</topic><topic>Akinesia</topic><topic>Congenital anomalies</topic><topic>Congenital defects</topic><topic>Cytogenetics</topic><topic>Defects</topic><topic>Deformation</topic><topic>DNA microarrays</topic><topic>DNA sequencing</topic><topic>Edema</topic><topic>Fetuses</topic><topic>Genetic analysis</topic><topic>Gestational age</topic><topic>Nucleotide sequence</topic><topic>Pregnancy</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dufke, Andreas</creatorcontrib><creatorcontrib>Hoopmann, Markus</creatorcontrib><creatorcontrib>Waldmüller, Stephan</creatorcontrib><creatorcontrib>Prodan, Natalia Carmen</creatorcontrib><creatorcontrib>Beck‐Wödl, Stefanie</creatorcontrib><creatorcontrib>Grasshoff, Ute</creatorcontrib><creatorcontrib>Heinrich, Tilman</creatorcontrib><creatorcontrib>Riess, Angelika</creatorcontrib><creatorcontrib>Kehrer, Martin</creatorcontrib><creatorcontrib>Falb, Ruth J.</creatorcontrib><creatorcontrib>Liebmann, Alexandra</creatorcontrib><creatorcontrib>Roggia, Cristiana</creatorcontrib><creatorcontrib>Stampfer, Miriam</creatorcontrib><creatorcontrib>Schadeck, Malou</creatorcontrib><creatorcontrib>Müller, Amelie J.</creatorcontrib><creatorcontrib>Grimmel, Mona</creatorcontrib><creatorcontrib>Stöbe, Petra</creatorcontrib><creatorcontrib>Gauck, Darja</creatorcontrib><creatorcontrib>Buchert‐Lo, Rebecca</creatorcontrib><creatorcontrib>Baumann, Sarah</creatorcontrib><creatorcontrib>Schäferhoff, Karin</creatorcontrib><creatorcontrib>Bertrand, Miriam</creatorcontrib><creatorcontrib>Menden, Benita</creatorcontrib><creatorcontrib>Sturm, Marc</creatorcontrib><creatorcontrib>Schütz, Leon</creatorcontrib><creatorcontrib>Riess, Olaf</creatorcontrib><creatorcontrib>Ossowski, Stephan</creatorcontrib><creatorcontrib>Haack, Tobias B.</creatorcontrib><creatorcontrib>Kagan, Karl Oliver</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Archive</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Prenatal diagnosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dufke, Andreas</au><au>Hoopmann, Markus</au><au>Waldmüller, Stephan</au><au>Prodan, Natalia Carmen</au><au>Beck‐Wödl, Stefanie</au><au>Grasshoff, Ute</au><au>Heinrich, Tilman</au><au>Riess, Angelika</au><au>Kehrer, Martin</au><au>Falb, Ruth J.</au><au>Liebmann, Alexandra</au><au>Roggia, Cristiana</au><au>Stampfer, Miriam</au><au>Schadeck, Malou</au><au>Müller, Amelie J.</au><au>Grimmel, Mona</au><au>Stöbe, Petra</au><au>Gauck, Darja</au><au>Buchert‐Lo, Rebecca</au><au>Baumann, Sarah</au><au>Schäferhoff, Karin</au><au>Bertrand, Miriam</au><au>Menden, Benita</au><au>Sturm, Marc</au><au>Schütz, Leon</au><au>Riess, Olaf</au><au>Ossowski, Stephan</au><au>Haack, Tobias B.</au><au>Kagan, Karl Oliver</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A single center experience of prenatal parent‐fetus trio exome sequencing for pregnancies with congenital anomalies</atitle><jtitle>Prenatal diagnosis</jtitle><addtitle>Prenat Diagn</addtitle><date>2022-06</date><risdate>2022</risdate><volume>42</volume><issue>7</issue><spage>901</spage><epage>910</epage><pages>901-910</pages><issn>0197-3851</issn><eissn>1097-0223</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Objectives
To examine the diagnostic yield of trio exome sequencing in fetuses with multiple structural defects with no pathogenic findings in cytogenetic and microarray analyses.
Methods
We recruited 51 fetuses with two or more defects, non‐immune fetal hydrops or fetal akinesia deformation syndrome|or fetal akinesia deformation sequence (FADS). Trio exome sequencing was performed on DNA from chorionic villi samples and parental blood. Detection of genomic variation and prioritization of clinically relevant variants was performed according to in‐house standard operating procedures.
Results
Median maternal and gestational age was 32.0 years and 21.0 weeks, respectively. Forty‐three (84.3%) fetuses had two or more affected organ systems. The remaining fetuses had isolated fetal hydrops or FADS. In total, the exome analysis established the genetic cause for the clinical abnormalities in 22 (43.1%, 95% CI 29.4%–57.8%) pregnancies.
Conclusions
In fetuses with multiple defects, hydrops or FADS and normal standard genetic results, trio exome sequencing has the potential to identify genetic anomalies in more than 40% of cases.
Key points
What's already known about this topic?
Genome‐wide sequencing for unspecific heterogeneous syndromic and non‐syndromic congenital conditions increases the diagnostic yield compared with standard genetic testing in both the pre‐ and postnatal settings. The diagnostic yield prenatally varies depending on selection criteria and number of anomalies present.
What does this study add?
Trio exome sequencing should be considered for fetuses with normal cytogenetic and micro‐array analysis and two or more organ defects, fetal hydrops or fetal akinesia syndromes. Selection of cases for exome sequencing should be based on expert prenatal imaging.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>35574990</pmid><doi>10.1002/pd.6170</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5616-5010</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0197-3851 |
| ispartof | Prenatal diagnosis, 2022-06, Vol.42 (7), p.901-910 |
| issn | 0197-3851 1097-0223 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2665112907 |
| source | Wiley |
| subjects | Abnormalities Akinesia Congenital anomalies Congenital defects Cytogenetics Defects Deformation DNA microarrays DNA sequencing Edema Fetuses Genetic analysis Gestational age Nucleotide sequence Pregnancy Zebrafish |
| title | A single center experience of prenatal parent‐fetus trio exome sequencing for pregnancies with congenital anomalies |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T21%3A21%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20single%20center%20experience%20of%20prenatal%20parent%E2%80%90fetus%20trio%20exome%20sequencing%20for%20pregnancies%20with%20congenital%20anomalies&rft.jtitle=Prenatal%20diagnosis&rft.au=Dufke,%20Andreas&rft.date=2022-06&rft.volume=42&rft.issue=7&rft.spage=901&rft.epage=910&rft.pages=901-910&rft.issn=0197-3851&rft.eissn=1097-0223&rft_id=info:doi/10.1002/pd.6170&rft_dat=%3Cproquest_cross%3E2676883374%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c3780-fb4c2b305255d76fee170f1ab6c2c5bde3b2f2a4a595b214946ce7bff530ca423%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2676883374&rft_id=info:pmid/35574990&rfr_iscdi=true |