{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:11:41Z","timestamp":1785449501852,"version":"3.56.0"},"reference-count":59,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 106-2314-B-182A-127 -MY3"],"award-info":[{"award-number":["MOST 106-2314-B-182A-127 -MY3"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005795","name":"Chang Gung Memorial Hospital, Linkou","doi-asserted-by":"publisher","award":["CMRPG3F0871"],"award-info":[{"award-number":["CMRPG3F0871"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hirschsprung's disease (HSCR) is a congenital disorder with the absence of myenteric and submucosal ganglion cells within distal gut. Due to multigenic inheritance and interactions, we employed next\u2010generation sequencing (NGS) to investigate genetic backgrounds of long\u2010segment HSCR (L\u2010HSCR) in Taiwan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genomic DNA extracted from peripheral blood of L\u2010HSCR patients was subjected to capture\u2010based NGS, based on a 31\u2010gene panel. The variants with allele frequency &lt;0.05 and predicted by computational methods as deleterious were further validated by Sanger sequencing in patients and their family as well to tell de novo from inherited variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between 2015\/04 and 2018\/05, this study enrolled 23 L\u2010HSCR patients, including 15 (65.2%) sporadic cases and 8 (34.8%) familial patients in 4 different families. Six sporadic and seven familial cases showed possible harmful variants across eight different genes, accounting for an overall detection rate of 56.5%. These variants mainly resided in <jats:italic>SEMA3C,<\/jats:italic> followed by <jats:italic>RET, NRG1,<\/jats:italic> and <jats:italic>NTRK1<\/jats:italic>. Three sporadic and 2 familial cases exhibited strong pathogenic variants as a deletional frameshift or stop codon in <jats:italic>RET, L1CAM<\/jats:italic> or <jats:italic>NRG1<\/jats:italic>. In a HSCR family, the father passed on a pathogenic <jats:italic>RET<\/jats:italic> frameshift to two daughters; however, only one developed HSCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Using NGS, we disclosed deleterious mutations such as a frameshift or stop codon in either familial or sporadic patients. Our cases with isolated L\u2010HSCR or even total colonic aganglionosis appeared to exhibit complex patterns of inheritance and incomplete penetrance even in families with the same genetic variants, reflecting the possible effects of environmental factors and genetic modifiers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13665","type":"journal-article","created":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T04:13:50Z","timestamp":1561522430000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Distinctive genetic variation of long\u2010segment Hirschsprung's disease in Taiwan"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5698-9645","authenticated-orcid":false,"given":"Wendy","family":"Yang","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine National Taiwan University Taipei Taiwan"},{"name":"Department of Surgery, College of Medicine, Chang Gung Children's Hospital Chang Gung University Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szu\u2010Chieh","family":"Chen","sequence":"additional","affiliation":[{"name":"Pediatric Research Center Chang Gung Children's Hospital Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Yao","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine, Chang Gung Children's Hospital Chang Gung University Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung\u2010Ching","family":"Ming","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine, Chang Gung Children's Hospital Chang Gung University Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeng\u2010Chang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine, Chang Gung Children's Hospital Chang Gung University Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Lung","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Genomics and Proteomics National Taiwan University Taipei Taiwan"},{"name":"Departments of Medical Genetics National Taiwan University Hospital Taipei Taiwan"},{"name":"Departments of Internal Medicine National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(49)90340-2"},{"issue":"2","key":"e_1_2_10_3_1","first-page":"212","article-title":"Resection of rectum and rectosigmoid with preservation of the sphincter for benign spastic lesions producing megacolon; an experimental study","volume":"24","author":"Swenson O","year":"1948","journal-title":"Surgery"},{"issue":"3","key":"e_1_2_10_4_1","first-page":"568","article-title":"A genetic study of Hirschsprung disease","volume":"46","author":"Badner JA","year":"1990","journal-title":"Am J Hum Genet"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.053959"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(51)92290-8"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1963.tb01983.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.25515"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(01)00012-0"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.15.4056"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85003"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90016-7"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-341"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0496-442"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(96)90170-0"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.8.670"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.116.1.167"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809630105"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.02.014"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0893-351"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng868"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.17"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2012.11.025"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12076"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1174-6"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2008.05.018"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2008.11.055"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21028"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0172947"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00360"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10252"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2008.02.076"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2008.00503.x"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-015-3732-x"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1086\/324343"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-014-3450-6"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt083"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-012-8392-4"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-009-2420-0"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1086\/515583"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2013.06.005"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1222"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35244"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.05.019"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14835-6"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054800"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-019-05605-7"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13550"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0922"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1159\/000371742"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036524"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-1035-4"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000001263"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2017.01.005"},{"issue":"11","key":"e_1_2_10_56_1","first-page":"2463","article-title":"Genomic organization of the human NTRK1 gene","volume":"13","author":"Greco A","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00092-1"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.230045.113"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200865"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10897-018-0264-2"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnmo.13665","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.13665","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nmo.13665","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.13665","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T23:54:01Z","timestamp":1694044441000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.13665"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,25]]},"references-count":59,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1111\/nmo.13665"],"URL":"https:\/\/doi.org\/10.1111\/nmo.13665","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,25]]},"assertion":[{"value":"2019-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13665"}}