{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T02:50:08Z","timestamp":1771555808728,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T00:00:00Z","timestamp":1602115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Megacystis\u2013microcolon\u2013intestinal hypoperistalsis syndrome (MMIHS), or \u201cvisceral myopathy,\u201d is a severe early onset disorder characterized by impaired muscle contractility in the bladder and intestines. Five genes are linked to MMIHS: primarily <jats:italic>ACTG2<\/jats:italic>, but also <jats:italic>LMOD1<\/jats:italic>, <jats:italic>MYH11<\/jats:italic>, <jats:italic>MYLK<\/jats:italic>, and <jats:italic>MYL9<\/jats:italic>. Here we describe a three\u2010year\u2010old girl with bilateral hydronephrosis diagnosed at 20\u00a0weeks gestation and congenital mydriasis (both of which have been previously observed among individuals with MMIHS). A clinical diagnosis of MMIHS was made based upon the presence of megacystis, lack of urinary bladder peristalsis, and intestinal pseudo\u2010obstruction. After initial testing of <jats:italic>ACTG2<\/jats:italic> was negative, further sequencing and deletion\/duplication testing was performed on the <jats:italic>LMOD1<\/jats:italic>, <jats:italic>MYH11<\/jats:italic>,<jats:italic>MYLK<\/jats:italic>, and <jats:italic>MYL9<\/jats:italic> genes. We identified two heterozygous loss of function variants in <jats:italic>MYL9<\/jats:italic>: an exon 4 deletion and a nine base pair deletion that removes the canonical splicing donor site at exon 2 (NM_006097.5:c.184+2_184+10del). Parental testing confirmed these variants to be <jats:italic>in trans<\/jats:italic> in our proband. To our knowledge, only one other individual with MMIHS has biallelic mutations in <jats:italic>MYL9<\/jats:italic> (a homozygous deletion encompassing exon 4). We suggest <jats:italic>MYL9<\/jats:italic> be targeted on genetic testing panels for MMIHS, smooth muscle myopathies, and cardiovascular phenotypes.<\/jats:p>","DOI":"10.1002\/mgg3.1516","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T18:47:13Z","timestamp":1602182833000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Compound heterozygous loss of function variants in <i>MYL9<\/i> in a child with megacystis\u2013microcolon\u2013intestinal hypoperistalsis syndrome"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3493-0818","authenticated-orcid":false,"given":"Justin L.","family":"Kandler","sequence":"first","affiliation":[{"name":"Fulgent Genetics Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgenia","family":"Sklirou","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Children's Hospital of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Woerner","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Children's Hospital of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"Walsh","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Children's Hospital of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleina","family":"Cox","sequence":"additional","affiliation":[{"name":"Fulgent Genetics Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Xue","sequence":"additional","affiliation":[{"name":"Fulgent Genetics Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00747"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.256"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.05.011"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1620507114"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12559"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00435a059"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301306"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8743874"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41749"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1833"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09708"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37857"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010017\u20100055\u20105"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20101473"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.168"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025855"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010013\u20101406\u20100"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004258"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1516","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1516","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1516","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T11:58:49Z","timestamp":1708516729000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,8]]},"references-count":19,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/mgg3.1516"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1516","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,8]]},"assertion":[{"value":"2020-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1516"}}