{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:48:15Z","timestamp":1785422895806,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009437","name":"Tel Aviv Sourasky Medical Center","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009437","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04nd58p63","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Laterality defects are rare congenital malformations that encompass congenital heart defects (CHDs) together with abnormalities of visceral organ arrangement (situs inversus or situs ambiguous). These defects may be isolated or part of a syndromic presentation with multisystem involvement. While over 50 genes have been implicated in laterality disorders, across multiple modes of inheritance, many cases remain molecularly undiagnosed. We sought to elucidate the molecular basis of dextrocardia, CHDs and visceral heterotaxy in two unrelated individuals of Arab-Muslim descent. Methods: Detailed clinical phenotyping and exome sequencing (ES) were performed for each of the probands, followed by familial segregation analysis. Results: ES revealed a shared homozygous variant in the Dan Domain Family Member 5 (DAND5) gene (NM_152654.3): c.396_397dup, p.(Tyr133SerfsTer11). DAND5 encodes a member of the Cerberus-related DAN protein family, which is involved in the establishment of left body asymmetry. This frameshift variant introduces a premature stop codon within the final exon, which is predicted to escape nonsense-mediated decay (NMD), resulting in a truncated protein lacking the functional DAN domain. Conclusions: DAND5 has recently been suggested as a candidate gene in heterotaxy and CHDs. Our findings further support biallelic loss of function variants in DAND5 autosomal recessive laterality defects.<\/jats:p>","DOI":"10.3390\/genes17080852","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Further Support for Association of DAND5 with Autosomal Recessive Laterality Disorders"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-0732","authenticated-orcid":false,"given":"Odelia","family":"Chorin","sequence":"first","affiliation":[{"name":"The Institute for Rare Diseases, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoav","family":"Bolkier","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"},{"name":"Pediatric Heart Institute, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7136-8027","authenticated-orcid":false,"given":"Uriel","family":"Katz","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"},{"name":"Pediatric Heart Institute, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishay","family":"Salem","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"},{"name":"Pediatric Heart Institute, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Anikster","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"},{"name":"Metabolic Disease Unit, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nechama","family":"Shalva","sequence":"additional","affiliation":[{"name":"Metabolic Disease Unit, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ortal","family":"Barel","sequence":"additional","affiliation":[{"name":"The Genomic Unit, Sheba Cancer Research Center, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8589-6920","authenticated-orcid":false,"given":"Moshe","family":"Giladi","sequence":"additional","affiliation":[{"name":"Internal Medicine D, Tel Aviv Sourasky Medical Center, Tel-Aviv 6423906, Israel"},{"name":"Department of Physiology and Pharmacology, Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rotem","family":"Semo-Oz","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"},{"name":"Department of Pediatrics B, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2038-7367","authenticated-orcid":false,"given":"Dror","family":"Ben-Ruby","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"},{"name":"Genetic Kidney Disease Research Laboratory, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly","family":"Lev-Hochberg","sequence":"additional","affiliation":[{"name":"The Institute for Rare Diseases, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadas","family":"Ityel","sequence":"additional","affiliation":[{"name":"The Institute for Rare Diseases, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lior","family":"Greenbaum","sequence":"additional","affiliation":[{"name":"The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asaf","family":"Vivante","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"},{"name":"Department of Pediatrics B, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Genetic Kidney Disease Research Laboratory, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Pediatric Nephrology Unit, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"The Talpiot Medical Leadership Program, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annick","family":"Rein-Rothschild","sequence":"additional","affiliation":[{"name":"The Institute for Rare Diseases, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Pode-Shakked","sequence":"additional","affiliation":[{"name":"The Institute for Rare Diseases, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel"},{"name":"The Talpiot Medical Leadership Program, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","first-page":"2241","article-title":"Birth prevalence of congenital heart disease worldwide: A systematic review and meta-analysis","volume":"15","author":"Konings","year":"2011","journal-title":"J. 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