The application of whole-exome sequencing in the early diagnosis of rare genetic diseases in children: a study from Southeastern China

Genetic diseases exhibit significant clinical and genetic diversity, leading to a complex and challenging diagnostic process. Exploiting novel approaches is imperative for the molecular diagnosis of genetic diseases. In this study, we utilized whole-exome sequencing (WES) to facilitate early diagnos...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in pediatrics 2024-10, Vol.12, p.1448895
Main Authors: Lai, Guihua, Gu, Qiying, Lai, Zhiyong, Chen, Haijun, Chen, Junkun, Huang, Jungao
Format: Article
Language:English
Subjects:
children
genetic diagnosis
genetic diseases
Pediatrics
rare disease
whole-exome sequencing
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites cdi_FETCH-LOGICAL-c348t-fa825953f1297a5c1acd1d7a4e5de880a0015b10ba8642302bfe7aa45539e9953
container_end_page
container_issue
container_start_page 1448895
container_title Frontiers in pediatrics
container_volume 12
creator Lai, Guihua
Gu, Qiying
Lai, Zhiyong
Chen, Haijun
Chen, Junkun
Huang, Jungao
description Genetic diseases exhibit significant clinical and genetic diversity, leading to a complex and challenging diagnostic process. Exploiting novel approaches is imperative for the molecular diagnosis of genetic diseases. In this study, we utilized whole-exome sequencing (WES) to facilitate early diagnosis in patients suspected of genetic disorders. This retrospective analysis included 144 patients diagnosed by singleton-WES Trio-WES between January 2021 and December 2023. We investigated the relevance of diagnosis rates with age, clinical presentation, and sample type. Among the 144 patients, 61 were diagnosed, yielding an overall diagnostic rate of 42.36%, with Trio-WES demonstrating a significantly higher diagnostic rate of 51.43% (36/70) compared to singleton-WES at 33.78% (25/74) (  
doi_str_mv 10.3389/fped.2024.1448895
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_76b9f874940e42a886dfc28cca7544da</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_76b9f874940e42a886dfc28cca7544da</doaj_id><sourcerecordid>3119726158</sourcerecordid><originalsourceid>FETCH-LOGICAL-c348t-fa825953f1297a5c1acd1d7a4e5de880a0015b10ba8642302bfe7aa45539e9953</originalsourceid><addsrcrecordid>eNpVks1uEzEUhUcIRKvSB2CDvGST4N8Zmw1CEdBKlVhQ1tYd-07iamIHe0LJC_DceJpQtZYlW77nfP47TfOW0aUQ2nwYduiXnHK5ZFJqbdSL5pxz0y64aOnLJ_Oz5rKUO1qb6ahi6nVzJoysXXbnzd_bDRLY7cbgYAopkjSQ-00acYF_0hZJwV97jC7ENQmRTFWMkMcD8QHWMZVQZkOGjGSNEafgaqUgFCyz3m3C6DPGjwRImfb-QIactuRH2lcSlAlzJKtNiPCmeTXAWPDyNF40P79-uV1dLW6-f7tefb5ZOCH1tBhAc2WUGBg3HSjHwHnmO5CoPGpNgVKmekZ70K3kgvJ-wA5AKiUMmmq8aK6PXJ_gzu5y2EI-2ATBPiykvLaQ6y1GtF3bm0F30kiKkoPWrR8c185Bp6T0UFmfjqzdvt-idxinDOMz6PNKDBu7Tr8tY9KIlslKeH8i5FSfuUx2G4rDcYSIaV-sYMx0vGVKVyk7Sl1OpWQcHvdh1M55sHMe7JwHe8pD9bx7esBHx__fF_8AvUi0Hw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3119726158</pqid></control><display><type>article</type><title>The application of whole-exome sequencing in the early diagnosis of rare genetic diseases in children: a study from Southeastern China</title><source>Open Access: PubMed Central</source><creator>Lai, Guihua ; Gu, Qiying ; Lai, Zhiyong ; Chen, Haijun ; Chen, Junkun ; Huang, Jungao</creator><creatorcontrib>Lai, Guihua ; Gu, Qiying ; Lai, Zhiyong ; Chen, Haijun ; Chen, Junkun ; Huang, Jungao</creatorcontrib><description>Genetic diseases exhibit significant clinical and genetic diversity, leading to a complex and challenging diagnostic process. Exploiting novel approaches is imperative for the molecular diagnosis of genetic diseases. In this study, we utilized whole-exome sequencing (WES) to facilitate early diagnosis in patients suspected of genetic disorders. This retrospective analysis included 144 patients diagnosed by singleton-WES Trio-WES between January 2021 and December 2023. We investigated the relevance of diagnosis rates with age, clinical presentation, and sample type. Among the 144 patients, 61 were diagnosed, yielding an overall diagnostic rate of 42.36%, with Trio-WES demonstrating a significantly higher diagnostic rate of 51.43% (36/70) compared to singleton-WES at 33.78% (25/74) (  &lt; 0.05). Global developmental delay had a diagnosis rate of 67.39%, significantly higher than muscular hypotonia at 30.43% (  &lt; 0.01) among different clinical phenotypic groups. Autosomal dominant disorders accounted for 70.49% (43/61) of positive cases, with autosomal abnormalities being fivefold more prevalent than sex chromosome abnormalities. Notably, sex chromosome abnormalities were more prevalent in males (80%, 8/10). Furthermore, 80.56% (29/36) of pathogenic variants were identified as mutations through Trio-WES. These findings highlight the effectiveness of WES in identifying genetic variants, and elucidating the molecular basis of genetic diseases, ultimately enabling early diagnosis in affected children.</description><identifier>ISSN: 2296-2360</identifier><identifier>EISSN: 2296-2360</identifier><identifier>DOI: 10.3389/fped.2024.1448895</identifier><identifier>PMID: 39439447</identifier><language>eng</language><publisher>Switzerland: Frontiers Media S.A</publisher><subject>children ; genetic diagnosis ; genetic diseases ; Pediatrics ; rare disease ; whole-exome sequencing</subject><ispartof>Frontiers in pediatrics, 2024-10, Vol.12, p.1448895</ispartof><rights>2024 Lai, Gu, Lai, Chen, Chen and Huang.</rights><rights>2024 Lai, Gu, Lai, Chen, Chen and Huang. 2024 Lai, Gu, Lai, Chen, Chen and Huang</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c348t-fa825953f1297a5c1acd1d7a4e5de880a0015b10ba8642302bfe7aa45539e9953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493614/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493614/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27900,27901,53765,53767</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39439447$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lai, Guihua</creatorcontrib><creatorcontrib>Gu, Qiying</creatorcontrib><creatorcontrib>Lai, Zhiyong</creatorcontrib><creatorcontrib>Chen, Haijun</creatorcontrib><creatorcontrib>Chen, Junkun</creatorcontrib><creatorcontrib>Huang, Jungao</creatorcontrib><title>The application of whole-exome sequencing in the early diagnosis of rare genetic diseases in children: a study from Southeastern China</title><title>Frontiers in pediatrics</title><addtitle>Front Pediatr</addtitle><description>Genetic diseases exhibit significant clinical and genetic diversity, leading to a complex and challenging diagnostic process. Exploiting novel approaches is imperative for the molecular diagnosis of genetic diseases. In this study, we utilized whole-exome sequencing (WES) to facilitate early diagnosis in patients suspected of genetic disorders. This retrospective analysis included 144 patients diagnosed by singleton-WES Trio-WES between January 2021 and December 2023. We investigated the relevance of diagnosis rates with age, clinical presentation, and sample type. Among the 144 patients, 61 were diagnosed, yielding an overall diagnostic rate of 42.36%, with Trio-WES demonstrating a significantly higher diagnostic rate of 51.43% (36/70) compared to singleton-WES at 33.78% (25/74) (  &lt; 0.05). Global developmental delay had a diagnosis rate of 67.39%, significantly higher than muscular hypotonia at 30.43% (  &lt; 0.01) among different clinical phenotypic groups. Autosomal dominant disorders accounted for 70.49% (43/61) of positive cases, with autosomal abnormalities being fivefold more prevalent than sex chromosome abnormalities. Notably, sex chromosome abnormalities were more prevalent in males (80%, 8/10). Furthermore, 80.56% (29/36) of pathogenic variants were identified as mutations through Trio-WES. These findings highlight the effectiveness of WES in identifying genetic variants, and elucidating the molecular basis of genetic diseases, ultimately enabling early diagnosis in affected children.</description><subject>children</subject><subject>genetic diagnosis</subject><subject>genetic diseases</subject><subject>Pediatrics</subject><subject>rare disease</subject><subject>whole-exome sequencing</subject><issn>2296-2360</issn><issn>2296-2360</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVks1uEzEUhUcIRKvSB2CDvGST4N8Zmw1CEdBKlVhQ1tYd-07iamIHe0LJC_DceJpQtZYlW77nfP47TfOW0aUQ2nwYduiXnHK5ZFJqbdSL5pxz0y64aOnLJ_Oz5rKUO1qb6ahi6nVzJoysXXbnzd_bDRLY7cbgYAopkjSQ-00acYF_0hZJwV97jC7ENQmRTFWMkMcD8QHWMZVQZkOGjGSNEafgaqUgFCyz3m3C6DPGjwRImfb-QIactuRH2lcSlAlzJKtNiPCmeTXAWPDyNF40P79-uV1dLW6-f7tefb5ZOCH1tBhAc2WUGBg3HSjHwHnmO5CoPGpNgVKmekZ70K3kgvJ-wA5AKiUMmmq8aK6PXJ_gzu5y2EI-2ATBPiykvLaQ6y1GtF3bm0F30kiKkoPWrR8c185Bp6T0UFmfjqzdvt-idxinDOMz6PNKDBu7Tr8tY9KIlslKeH8i5FSfuUx2G4rDcYSIaV-sYMx0vGVKVyk7Sl1OpWQcHvdh1M55sHMe7JwHe8pD9bx7esBHx__fF_8AvUi0Hw</recordid><startdate>20241008</startdate><enddate>20241008</enddate><creator>Lai, Guihua</creator><creator>Gu, Qiying</creator><creator>Lai, Zhiyong</creator><creator>Chen, Haijun</creator><creator>Chen, Junkun</creator><creator>Huang, Jungao</creator><general>Frontiers Media S.A</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20241008</creationdate><title>The application of whole-exome sequencing in the early diagnosis of rare genetic diseases in children: a study from Southeastern China</title><author>Lai, Guihua ; Gu, Qiying ; Lai, Zhiyong ; Chen, Haijun ; Chen, Junkun ; Huang, Jungao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c348t-fa825953f1297a5c1acd1d7a4e5de880a0015b10ba8642302bfe7aa45539e9953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>children</topic><topic>genetic diagnosis</topic><topic>genetic diseases</topic><topic>Pediatrics</topic><topic>rare disease</topic><topic>whole-exome sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lai, Guihua</creatorcontrib><creatorcontrib>Gu, Qiying</creatorcontrib><creatorcontrib>Lai, Zhiyong</creatorcontrib><creatorcontrib>Chen, Haijun</creatorcontrib><creatorcontrib>Chen, Junkun</creatorcontrib><creatorcontrib>Huang, Jungao</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Frontiers in pediatrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lai, Guihua</au><au>Gu, Qiying</au><au>Lai, Zhiyong</au><au>Chen, Haijun</au><au>Chen, Junkun</au><au>Huang, Jungao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The application of whole-exome sequencing in the early diagnosis of rare genetic diseases in children: a study from Southeastern China</atitle><jtitle>Frontiers in pediatrics</jtitle><addtitle>Front Pediatr</addtitle><date>2024-10-08</date><risdate>2024</risdate><volume>12</volume><spage>1448895</spage><pages>1448895-</pages><issn>2296-2360</issn><eissn>2296-2360</eissn><abstract>Genetic diseases exhibit significant clinical and genetic diversity, leading to a complex and challenging diagnostic process. Exploiting novel approaches is imperative for the molecular diagnosis of genetic diseases. In this study, we utilized whole-exome sequencing (WES) to facilitate early diagnosis in patients suspected of genetic disorders. This retrospective analysis included 144 patients diagnosed by singleton-WES Trio-WES between January 2021 and December 2023. We investigated the relevance of diagnosis rates with age, clinical presentation, and sample type. Among the 144 patients, 61 were diagnosed, yielding an overall diagnostic rate of 42.36%, with Trio-WES demonstrating a significantly higher diagnostic rate of 51.43% (36/70) compared to singleton-WES at 33.78% (25/74) (  &lt; 0.05). Global developmental delay had a diagnosis rate of 67.39%, significantly higher than muscular hypotonia at 30.43% (  &lt; 0.01) among different clinical phenotypic groups. Autosomal dominant disorders accounted for 70.49% (43/61) of positive cases, with autosomal abnormalities being fivefold more prevalent than sex chromosome abnormalities. Notably, sex chromosome abnormalities were more prevalent in males (80%, 8/10). Furthermore, 80.56% (29/36) of pathogenic variants were identified as mutations through Trio-WES. These findings highlight the effectiveness of WES in identifying genetic variants, and elucidating the molecular basis of genetic diseases, ultimately enabling early diagnosis in affected children.</abstract><cop>Switzerland</cop><pub>Frontiers Media S.A</pub><pmid>39439447</pmid><doi>10.3389/fped.2024.1448895</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2296-2360
ispartof Frontiers in pediatrics, 2024-10, Vol.12, p.1448895
issn 2296-2360
2296-2360
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_76b9f874940e42a886dfc28cca7544da
source Open Access: PubMed Central
subjects children
genetic diagnosis
genetic diseases
Pediatrics
rare disease
whole-exome sequencing
title The application of whole-exome sequencing in the early diagnosis of rare genetic diseases in children: a study from Southeastern China
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-24T11%3A39%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20application%20of%20whole-exome%20sequencing%20in%20the%20early%20diagnosis%20of%20rare%20genetic%20diseases%20in%20children:%20a%20study%20from%20Southeastern%20China&rft.jtitle=Frontiers%20in%20pediatrics&rft.au=Lai,%20Guihua&rft.date=2024-10-08&rft.volume=12&rft.spage=1448895&rft.pages=1448895-&rft.issn=2296-2360&rft.eissn=2296-2360&rft_id=info:doi/10.3389/fped.2024.1448895&rft_dat=%3Cproquest_doaj_%3E3119726158%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c348t-fa825953f1297a5c1acd1d7a4e5de880a0015b10ba8642302bfe7aa45539e9953%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=3119726158&rft_id=info:pmid/39439447&rfr_iscdi=true