{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:48:42Z","timestamp":1790732922532,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations of the thyroid hormone receptor interactor 11 gene (<jats:italic>TRIP11<\/jats:italic>, OMIM: 604505) at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.omim.org\/geneMap\/14\/422?start=-3%26limit=10%26highlight=422\">14q32.12<\/jats:ext-link> have been associated with the autosomal recessive achondrogenesis type IA (ACG1A, OMIM: 200600) or osteochondrodysplasia (ODCD, OMIM: 184260). In this clinical report of a Chinese family, the mother had two consecutive pregnancies with similar aberrant phenotypes in the fetuses showing severe limb shortening. Whole exome sequencing (WES) of DNA from the second fetus identified a heterozygous frameshift mutation (NM_004239: c.3852delT) of <jats:italic>TRIP11<\/jats:italic>. Although this was consistent with the fetal clinical phenotypes, initial review of the WES results implied another novel mutation. To test this, we used high\u2010precision clinical exome sequencing (HPCES) and found a mutation in Intron 18 of <jats:italic>TRIP11<\/jats:italic> (c.5457+77T&gt;G). Moreover, the sequencing depth of this mutation was only 3\u00d7 that of WES compared with 161\u00d7 that by HPCES. To ascertain the pathogenesis of the mutation (c.5457+77T&gt;G), RT\u2010PCR conducted using the parents' blood samples showed a 77\u2010bp intronic sequence in the transcripts, which might have encoded for a shortened protein because of early termination due to code shifting. Our study furthers current understanding of deep intron function and provides a novel diagnostic method of deep intragenic mutations in families having two or more consecutive pregnancies with similar aberrant fetal phenotypes.<\/jats:p>","DOI":"10.1002\/ajmg.a.62260","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T12:29:44Z","timestamp":1621513784000},"page":"2482-2487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel deep intronic and frameshift mutations causing a <scp><i>TRIP11<\/i><\/scp>\u2010related disorder"],"prefix":"10.1002","volume":"185","author":[{"given":"Yeqing","family":"Qian","sequence":"first","affiliation":[{"name":"Women's Hospital School of Medicine, Zhejiang University  Zhejiang China"},{"name":"Key Laboratory of Reproductive Genetics (Zhejiang University) Ministry of Education, 1, Xueshi Road  Zhejiang 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