{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T14:31:32Z","timestamp":1780929092979,"version":"3.54.1"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T00:00:00Z","timestamp":1526860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1002147"],"award-info":[{"award-number":["APP1002147"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1122952"],"award-info":[{"award-number":["APP1122952"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1117510"],"award-info":[{"award-number":["APP1117510"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2018,9]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Primary chronic intestinal pseudo\u2010obstruction (CIPO) is a rare, potentially life\u2010threatening disorder characterized by severely impaired gastrointestinal motility. The objective of this study was to examine the contribution of ACTG<\/jats:styled-content>2<\/jats:italic>, LMOD<\/jats:styled-content>1<\/jats:italic>, MYH<\/jats:styled-content>11,<\/jats:italic> and MYLK<\/jats:styled-content><\/jats:italic> mutations in an Australasian cohort of patients with a diagnosis of primary CIPO associated with visceral myopathy.<\/jats:p><\/jats:sec>Methods<\/jats:title>Pediatric and adult patients with primary CIPO and suspected visceral myopathy were recruited from across Australia and New Zealand. Sanger sequencing of the genes encoding enteric gamma\u2010actin (ACTG<\/jats:styled-content>2<\/jats:italic>) and smooth muscle leiomodin (LMOD<\/jats:styled-content>1) was performed on DNA<\/jats:styled-content> from patients, and their relatives, where available. MYH<\/jats:styled-content>11<\/jats:italic> and MYLK<\/jats:styled-content><\/jats:italic> were screened by next\u2010generation sequencing.<\/jats:p><\/jats:sec>Key results<\/jats:title>We identified heterozygous missense variants in ACTG<\/jats:styled-content>2<\/jats:italic> in 7 of 17 families (~41%) diagnosed with CIPO and its associated conditions. We also identified a previously unpublished missense mutation (c.443C>T, p.Arg148Leu) in one family. One case presented with megacystis\u2010microcolon\u2010intestinal hypoperistalsis syndrome in utero<\/jats:italic> with subsequent termination of pregnancy at 28\u00a0weeks' gestation. All of the substitutions identified occurred at arginine residues. No likely pathogenic variants in LMOD<\/jats:styled-content>1<\/jats:italic>, MYH<\/jats:styled-content>11,<\/jats:italic> or MYLK<\/jats:styled-content><\/jats:italic> were identified within our cohort.<\/jats:p><\/jats:sec>Conclusions and inferences<\/jats:title>ACTG<\/jats:styled-content>2<\/jats:italic> mutations represent a significant underlying cause of primary CIPO with visceral myopathy and associated phenotypes in Australasian patients. Thus, ACTG<\/jats:styled-content>2<\/jats:italic> sequencing should be considered in cases presenting with hypoperistalsis phenotypes with suspected visceral myopathy. It is likely that variants in other genes encoding enteric smooth muscle contractile proteins will contribute further to the genetic heterogeneity of hypoperistalsis phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13371","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T07:49:14Z","timestamp":1526888954000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Variants in ACTG<\/scp>2<\/i> underlie a substantial number of Australasian patients with primary chronic intestinal pseudo\u2010obstruction"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3634-211X","authenticated-orcid":false,"given":"G.","family":"Ravenscroft","sequence":"first","affiliation":[{"name":"Harry Perkins Institute of Medical Research University of Western Australia Nedlands WA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Pannell","sequence":"additional","affiliation":[{"name":"Harry Perkins Institute of Medical Research University of Western Australia Nedlands WA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"O'Grady","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Ong","sequence":"additional","affiliation":[{"name":"Harry Perkins Institute of Medical Research University of Western Australia Nedlands WA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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