{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:22:19Z","timestamp":1777040539040,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,20]],"date-time":"2019-01-20T00:00:00Z","timestamp":1547942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK115950"],"award-info":[{"award-number":["R01-DK115950"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK67071"],"award-info":[{"award-number":["R01-DK67071"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We identified a pedigree over five generations with 49 members, some of whom had chronic megacolon presenting in adolescence or adulthood. We aimed to assess the genetic cause of chronic megacolon through clinical and DNA studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>After ethical approval and informed consent, family members provided answers to standard bowel disease questionnaires, radiological or surgical records, and DNA (buccal mucosal scraping). Exome DNA sequencing of colon tissue or blood DNA from seven family members with colon or duodenal dilatation, or no megacolon (n\u00a0=\u00a01) was carried out. Sanger sequencing was performed in 22 additional family members to further evaluate candidate variants. The study focused on genes of potential relevance to enteric nerve (ENS) maturation and Hirschsprung's disease or megacolon, based on the literature (<jats:italic>GFRA1<\/jats:italic>, <jats:italic>NKX2\u20101<\/jats:italic>, <jats:italic>KIF26A<\/jats:italic>, <jats:italic>TPM3<\/jats:italic>, <jats:italic>ACTG2<\/jats:italic>, <jats:italic>SCN10A<\/jats:italic>, and <jats:italic>C17orf107<\/jats:italic> [<jats:italic>CHRNE<\/jats:italic>]) and other genetic variants that co\u2010segregated with megacolon in the six affected family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Information was available in all except five members alive at time of study; among 30 members who provided DNA, six had definite megacolon, one megaduodenum, seven significant constipation without bowel dilatation, and 16 normal bowel function by questionnaire. Among genes studied, <jats:italic>SEMA3F<\/jats:italic> (g.3:50225360A&gt;G; c1873A&gt;G) was found in 6\/6 family members with megacolon. The <jats:italic>SEMA3F<\/jats:italic> gene variant was assessed as potentially pathogenic, based on M\u2010CAP in silico prediction. <jats:italic>SEMA3F<\/jats:italic> function is associated with genes (<jats:italic>KIT<\/jats:italic> and <jats:italic>PDGFRB<\/jats:italic>) that impact intestinal pacemaker function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Familial chronic megacolon appears to be associated with <jats:italic>SEMA3F<\/jats:italic>, which is associated with genes impacting enteric nerve or pacemaker function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13550","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T02:59:32Z","timestamp":1548039572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Familial chronic megacolon presenting in childhood or adulthood: Seeking the presumed gene association"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6472-7514","authenticated-orcid":false,"given":"Michael","family":"Camilleri","sequence":"first","affiliation":[{"name":"Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Wieben","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Eckert","sequence":"additional","affiliation":[{"name":"Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Carlson","sequence":"additional","affiliation":[{"name":"Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph","family":"Hurley O\u2019Dwyer","sequence":"additional","affiliation":[{"name":"Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) 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