{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T22:21:33Z","timestamp":1740176493598,"version":"3.37.3"},"reference-count":11,"publisher":"Cold Spring Harbor Laboratory","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"accepted":{"date-parts":[[2022,10,25]]},"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:p>The majority of heterotaxy cases do not obtain a molecular diagnosis, although pathogenic variants in more than 50 genes are known to cause heterotaxy. A heterozygous missense variant in<jats:italic>DAND5<\/jats:italic>, a nodal inhibitor, which functions in early development for establishment of right\u2013left patterning, has been implicated in heterotaxy. Recently, the first case was reported of a<jats:italic>DAND5<\/jats:italic>biallelic loss-of-function (LoF) variant in an individual with heterotaxy. Here, we describe a second unrelated individual with heterotaxy syndrome and a homozygous frameshift variant in<jats:italic>DAND5<\/jats:italic>(NM_152654.2:c.197del [p.Leu66ArgfsTer22]). Using an in vitro assay, we demonstrate that the<jats:italic>DAND5<\/jats:italic>c.197del variant is unable to inhibit nodal signaling when compared with the wild-type expression construct. This work strengthens the genetic and functional evidence for biallelic LoF variants in<jats:italic>DAND5<\/jats:italic>causing an autosomal recessive heterotaxy syndrome.<\/jats:p>","DOI":"10.1101\/mcs.a006248","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T21:05:38Z","timestamp":1667250338000},"page":"a006248","source":"Crossref","is-referenced-by-count":0,"title":["A novel biallelic loss-of-function variant in<i>DAND5<\/i>causes heterotaxy syndrome"],"prefix":"10.1101","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2834-0843","authenticated-orcid":false,"given":"Mythily","family":"Ganapathi","sequence":"first","affiliation":[]},{"given":"Christie M.","family":"Buchovecky","sequence":"additional","affiliation":[]},{"given":"Fernando","family":"Cristo","sequence":"additional","affiliation":[]},{"given":"Priyanka","family":"Ahimaz","sequence":"additional","affiliation":[]},{"given":"Carrie","family":"Ruzal-Shapiro","sequence":"additional","affiliation":[]},{"given":"Karen","family":"Wou","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 M.","family":"In\u00e1cio","sequence":"additional","affiliation":[]},{"given":"Alejandro","family":"Iglesias","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 A.","family":"Belo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0962-7873","authenticated-orcid":false,"given":"Vaidehi","family":"Jobanputra","sequence":"additional","affiliation":[]}],"member":"246","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"2024102313300890000_8.7.a006248.1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102716"},{"key":"2024102313300890000_8.7.a006248.2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2021-107775"},{"key":"2024102313300890000_8.7.a006248.3","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-017-0444-1"},{"key":"2024102313300890000_8.7.a006248.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2017.10.019"},{"key":"2024102313300890000_8.7.a006248.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-13026-2"},{"key":"2024102313300890000_8.7.a006248.6","doi-asserted-by":"publisher","DOI":"10.1101\/gad.306504"},{"key":"2024102313300890000_8.7.a006248.7","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2024102313300890000_8.7.a006248.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00970-4"},{"key":"2024102313300890000_8.7.a006248.9","doi-asserted-by":"publisher","DOI":"10.1242\/dev.000901"},{"key":"2024102313300890000_8.7.a006248.10","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.187302"},{"key":"2024102313300890000_8.7.a006248.11","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.13.4439-4449.2002"}],"container-title":["Molecular Case Studies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/mcs.a006248","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T20:30:18Z","timestamp":1729715418000},"score":1,"resource":{"primary":{"URL":"http:\/\/molecularcasestudies.cshlp.org\/lookup\/doi\/10.1101\/mcs.a006248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,31]]},"references-count":11,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,12,28]]},"published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1101\/mcs.a006248"],"URL":"https:\/\/doi.org\/10.1101\/mcs.a006248","relation":{},"ISSN":["2373-2865","2373-2873"],"issn-type":[{"type":"print","value":"2373-2865"},{"type":"electronic","value":"2373-2873"}],"subject":[],"published":{"date-parts":[[2022,10,31]]}}}