{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:53:51Z","timestamp":1789764831557,"version":"4.0.1"},"reference-count":25,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2011,2,13]]},"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare condition defined by eyelid colobomas, cryptophthalmos and anophthalmia\/microphthalmia, an aberrant hairline, a bifid or broad nasal tip, and gastrointestinal anomalies such as omphalocele and anal stenosis. Autosomal recessive inheritance had been assumed because of consanguinity in the Oji-Cre population of Manitoba and reports of affected siblings, but no locus or cytogenetic aberration had previously been described.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>This study shows that MOTA syndrome is caused by mutations in <jats:italic>FREM1<\/jats:italic>, a gene previously mutated in bifid nose, renal agenesis, and anorectal malformations (BNAR) syndrome. MOTA syndrome and BNAR syndrome can therefore be considered as part of a phenotypic spectrum that is similar to, but distinct from and less severe than, Fraser syndrome. Re-examination of <jats:italic>Frem1<jats:sup>bat\/bat<\/jats:sup>\n                     <\/jats:italic> mutant mice found new evidence that <jats:italic>Frem1<\/jats:italic> is involved in anal and craniofacial development, with anal prolapse, eyelid colobomas, telecanthus, a shortened snout and reduced philtral height present in the mutant mice, similar to the human phenotype in MOTA syndrome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The milder phenotypes associated with <jats:italic>FREM1<\/jats:italic> deficiency in humans (MOTA syndrome and BNAR syndrome) compared to that resulting from <jats:italic>FRAS1<\/jats:italic> and <jats:italic>FREM2<\/jats:italic> loss of function (Fraser syndrome) are also consistent with the less severe phenotypes resulting from <jats:italic>Frem1<\/jats:italic> loss of function in mice. Together, Fraser, BNAR and MOTA syndromes constitute a clinically overlapping group of FRAS\u2013FREM complex diseases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2011.089631","type":"journal-article","created":{"date-parts":[[2011,4,21]],"date-time":"2011-04-21T01:12:51Z","timestamp":1303348371000},"page":"375-382","source":"Crossref","is-referenced-by-count":67,"title":["Manitoba-oculo-tricho-anal (MOTA) syndrome is caused by mutations in <i>FREM1<\/i>"],"prefix":"10.1136","volume":"48","author":[{"given":"Anne M","family":"Slavotinek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio E","family":"Baranzini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denny","family":"Schanze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandre","family":"Labelle-Dumais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieran M","family":"Short","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mani","family":"Yahyavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia K","family":"Bijlsma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Musone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashleigh","family":"Wheatley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pui-Yan","family":"Kwok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Marles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Fryns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Murat","family":"Maga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed G","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B","family":"Gould","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lohith","family":"Madireddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chumei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy C","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Smyth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert E","family":"Chudley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Zenker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2011,4,20]]},"reference":[{"key":"2025101715165499000_48.6.375.1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320420609"},{"key":"2025101715165499000_48.6.375.2","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/ajmg.a.31446","article-title":"Manitoba Oculotrichoanal (MOTA) syndrome: report of eight new cases","volume":"143A","author":"Li","year":"2007","journal-title":"Am J Med Genet A"},{"key":"2025101715165499000_48.6.375.3","unstructured":"Li C . 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