{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T21:56:55Z","timestamp":1793224615670,"version":"4.5.0"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"am","delay-in-days":331,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL 134599"],"award-info":[{"award-number":["P01 HL 134599"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["AHA19TPA34850054"],"award-info":[{"award-number":["AHA19TPA34850054"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006733","name":"Indiana University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006733","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmn.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Current Opinion in Genetics &amp; Development"],"published-print":{"date-parts":[[2022,8]]},"DOI":"10.1016\/j.gde.2022.101937","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:05:06Z","timestamp":1656374706000},"page":"101937","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":26,"special_numbering":"C","title":["The genetic landscape of cardiovascular left\u2013right patterning defects"],"prefix":"10.1016","volume":"75","author":[{"given":"John R","family":"Wells","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria B","family":"Padua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M","family":"Ware","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.gde.2022.101937_bib1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1161\/CIRCULATIONAHA.109.857987","article-title":"Recurrence of congenital heart defects in families","volume":"120","author":"\u00d8yen","year":"2009","journal-title":"Circulation"},{"key":"10.1016\/j.gde.2022.101937_bib2","doi-asserted-by":"crossref","first-page":"e653","DOI":"10.1161\/CIR.0000000000000606","article-title":"Genetic basis for congenital heart disease: revisited: a scientific statement from the American Heart Association","volume":"138","author":"Pierpont","year":"2018","journal-title":"Circulation"},{"key":"10.1016\/j.gde.2022.101937_bib3","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1002\/ajmg.a.36695","article-title":"Laterality defects in the national birth defects prevention study (1998-2007): birth prevalence and descriptive epidemiology","volume":"164A","author":"Lin","year":"2014","journal-title":"Am J Med Genet Part A"},{"key":"10.1016\/j.gde.2022.101937_bib4","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1016\/j.jaci.2016.10.014","article-title":"Heterotaxy syndrome with and without spleen: different infection risk and management","volume":"139","author":"Piano Mortari","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.gde.2022.101937_bib5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1086\/380998","article-title":"Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects","volume":"74","author":"Ware","year":"2004","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.gde.2022.101937_bib6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.semcdb.2020.06.003","article-title":"Right, left and cilia: how asymmetry is established","volume":"110","author":"Little","year":"2021","journal-title":"Semin Cell Dev Biol"},{"key":"10.1016\/j.gde.2022.101937_bib7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/nature00849","article-title":"Determination of left\u2013right patterning of the mouse embryo by artificial nodal flow","volume":"418","author":"Nonaka","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.gde.2022.101937_bib8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1005821","article-title":"DNAH6 and its interactions with PCD genes in heterotaxy and primary ciliary dyskinesia","volume":"12","author":"Li","year":"2016","journal-title":"PLoS Genet"},{"key":"10.1016\/j.gde.2022.101937_bib9","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00795-021-00287-5","article-title":"Whole-exome sequencing reveals a combination of extremely rare single-nucleotide polymorphism of DNAH9 and RSPH1 genes in a Japanese fetus with situs viscerum inversus","volume":"54","author":"Tate","year":"2021","journal-title":"Med Mol Morphol"},{"key":"10.1016\/j.gde.2022.101937_bib10","article-title":"DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome","volume":"9","author":"Liu","year":"2019","journal-title":"Sci Rep"},{"key":"10.1016\/j.gde.2022.101937_bib11","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ceb.2019.09.002","article-title":"Planar cell polarity signaling in the development of left\u2013right asymmetry","volume":"62","author":"Axelrod","year":"2020","journal-title":"Curr Opin Cell Biol"},{"key":"10.1016\/j.gde.2022.101937_bib12","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2011-12-9-r91","article-title":"SHROOM3 is a novel candidate for heterotaxy identified by whole exome sequencing","volume":"12","author":"Tariq","year":"2011","journal-title":"Genome Biol"},{"key":"10.1016\/j.gde.2022.101937_bib13","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/978-981-10-7311-3_15","article-title":"ZIC3 in heterotaxy","volume":"1046","author":"Bellchambers","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"10.1016\/j.gde.2022.101937_bib14","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/S0092-8674(00)81537-8","article-title":"Shroom, a PDZ domain\u2013containing actin-binding protein, is required for neural tube morphogenesis in mice","volume":"99","author":"Hildebrand","year":"1999","journal-title":"Cell"},{"key":"10.1016\/j.gde.2022.101937_bib15","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1242\/bio.20149589","article-title":"Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure","volume":"4","author":"McGreevy","year":"2015","journal-title":"Biol Open"},{"key":"10.1016\/j.gde.2022.101937_bib16","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ydbio.2020.05.013","article-title":"SHROOM3 is downstream of the planar cell polarity pathway and loss-of-function results in congenital heart defects","volume":"464","author":"Durbin","year":"2020","journal-title":"Dev Biol"},{"key":"10.1016\/j.gde.2022.101937_bib17","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ydbio.2012.01.011","article-title":"An essential and highly conserved role for Zic3 in left\u2013right patterning, gastrulation and convergent extension morphogenesis","volume":"364","author":"Cast","year":"2012","journal-title":"Dev Biol"},{"issue":"24","key":"10.1016\/j.gde.2022.101937_bib18","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1093\/hmg\/ddab195","article-title":"Loss of Zic3 impairs planar cell polarity leading to abnormal left\u2013right signaling, heart defects and neural tube defects","volume":"30","author":"Bellchambers","year":"2021","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.gde.2022.101937_bib19","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.724826","article-title":"Novel MYO1D missense variant identified through whole exome sequencing and computational biology analysis expands the spectrum of causal genes of laterality defects","volume":"8","author":"Alsafwani","year":"2021","journal-title":"Front Med"},{"key":"10.1016\/j.gde.2022.101937_bib20","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/nature04625","article-title":"An unconventional myosin in Drosophila reverses the default handedness in visceral organs","volume":"440","author":"Hozumi","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.gde.2022.101937_bib21","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nature04623","article-title":"Type ID unconventional myosin controls left\u2013right asymmetry in Drosophila","volume":"440","author":"Sp\u00e9der","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.gde.2022.101937_bib22","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-05866-2","article-title":"Vertebrate myosin 1d regulates left\u2013right organizer morphogenesis and laterality","volume":"9","author":"Saydmohammed","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.gde.2022.101937_bib23","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.cub.2018.01.075","article-title":"A conserved role of the unconventional myosin 1d in laterality determination","volume":"28","author":"Tingler","year":"2018","journal-title":"Curr Biol"},{"key":"10.1016\/j.gde.2022.101937_bib24","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-04284-8","article-title":"Myosin1D is an evolutionarily conserved regulator of animal left\u2013right asymmetry","volume":"9","author":"Juan","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.gde.2022.101937_bib25","doi-asserted-by":"crossref","DOI":"10.1186\/s12881-017-0444-1","article-title":"Functional study of DAND5 variant in patients with congenital heart disease and laterality defects","volume":"18","author":"Cristo","year":"2017","journal-title":"BMC Med Genet"},{"key":"10.1016\/j.gde.2022.101937_bib26","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1002\/ajmg.a.61509","article-title":"A founder truncating variant in GDF1 causes autosomal-recessive right isomerism and associated congenital heart defects in multiplex Arab kindreds","volume":"182","author":"Marek-Yagel","year":"2020","journal-title":"Am J Med Genet Part A"},{"key":"10.1016\/j.gde.2022.101937_bib27","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/s41431-018-0307-z","article-title":"Genetic architecture of laterality defects revealed by whole exome sequencing","volume":"27","author":"Li","year":"2019","journal-title":"Eur J Hum Genet"},{"key":"10.1016\/j.gde.2022.101937_sbref28","article-title":"Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects","author":"Bolkier","year":"2021","journal-title":"J Med Genet"},{"key":"10.1016\/j.gde.2022.101937_sbref29","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-24295-2","article-title":"Fluid flow-induced left\u2013right asymmetric Dand5 mRNA in the mouse embryo requires a Bicc1-Ccr4 RNA degradation complex","volume":"12","author":"Minegishi","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.gde.2022.101937_sbref30","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-25464-z","article-title":"Bicc1 and Dicer regulate left\u2013right patterning through post-transcriptional control of the Nodal inhibitor Dand5","volume":"12","author":"Maerker","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.gde.2022.101937_bib31","article-title":"Bi-allelic mutations in NUP205 and NUP210 are associated with abnormal cardiac left\u2013right patterning","volume":"12","author":"Chen","year":"2019","journal-title":"Circ: Genomic Precis Med"},{"key":"10.1016\/j.gde.2022.101937_bib32","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.devcel.2016.08.002","article-title":"Congenital heart disease genetics uncovers context-dependent organization and function of nucleoporins at cilia","volume":"38","author":"del Viso","year":"2016","journal-title":"Dev Cell"},{"key":"10.1016\/j.gde.2022.101937_sbref33","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ydbio.2020.10.001","article-title":"Nucleoporin NUP205 plays a critical role in cilia and congenital disease","volume":"469","author":"Marquez","year":"2021","journal-title":"Dev Biol"},{"key":"10.1016\/j.gde.2022.101937_bib34","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1073\/pnas.1019645108","article-title":"Rare copy number variations in congenital heart disease patients identify unique genes in left\u2013right patterning","volume":"108","author":"Fakhro","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.gde.2022.101937_bib35","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-020-03214-1","article-title":"Biallelic loss of function NEK3 mutations deacetylate \u03b1-tubulin and downregulate NUP205 that predispose individuals to cilia-related abnormal cardiac left\u2013right patterning","volume":"11","author":"Zhang","year":"2020","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.gde.2022.101937_sbref36","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1002\/humu.24132","article-title":"Next-generation sequencing in a series of 80 fetuses with complex cardiac malformations and\/or heterotaxy","volume":"41","author":"Liu","year":"2020","journal-title":"Hum Mut"},{"key":"10.1016\/j.gde.2022.101937_bib37","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1681\/ASN.2012050490","article-title":"Loss of the ciliary kinase Nek8 causes left\u2013right asymmetry defects","volume":"24","author":"Manning","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"10.1016\/j.gde.2022.101937_bib38","first-page":"4068","article-title":"The NIMA-like kinase Nek2 is a key switch balancing cilia biogenesis and resorption in the development of left\u2013right asymmetry","volume":"142","author":"Endicott","year":"2015","journal-title":"Development"},{"key":"10.1016\/j.gde.2022.101937_sbref39","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1172\/JCI98890","article-title":"Imbalanced mitochondrial function provokes heterotaxy via aberrant ciliogenesis","volume":"129","author":"Burkhalter","year":"2019","journal-title":"J Clin Invest"},{"key":"10.1016\/j.gde.2022.101937_bib40","doi-asserted-by":"crossref","first-page":"176.e1","DOI":"10.1016\/j.ajog.2019.08.028","article-title":"Specific birth defects in pregnancies of women with diabetes: National Birth Defects Prevention Study, 1997\u20132011","volume":"222","author":"Tinker","year":"2020","journal-title":"Am J Obstet Gynecol"},{"key":"10.1016\/j.gde.2022.101937_bib41","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/nep.13008","article-title":"Mutations in TTC21B cause different phenotypes in two childhood cases in China","volume":"23","author":"Zhang","year":"2018","journal-title":"Nephrology"},{"key":"10.1016\/j.gde.2022.101937_bib42","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1002\/ajmg.a.62093","article-title":"A novel heterotaxy gene: expansion of the phenotype of TTC21B-spectrum disease","volume":"185","author":"Strong","year":"2021","journal-title":"Am J Med Genet Part A"},{"key":"10.1016\/j.gde.2022.101937_bib43","doi-asserted-by":"crossref","DOI":"10.1098\/rstb.2015.0406","article-title":"Copy number variation as a genetic basis for heterotaxy and heterotaxy-spectrum congenital heart defects","volume":"371","author":"Cowan","year":"2016","journal-title":"Phil Trans R Soc B"},{"key":"10.1016\/j.gde.2022.101937_sbref44","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ydbio.2019.12.014","article-title":"Loss of ciliary transition zone protein TMEM107 leads to heterotaxy in mice","volume":"460","author":"Shylo","year":"2020","journal-title":"Dev Biol"},{"key":"10.1016\/j.gde.2022.101937_bib45","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nbt.1644","article-title":"A mouse knockout library for secreted and transmembrane proteins","volume":"28","author":"Tang","year":"2010","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.gde.2022.101937_bib46","article-title":"Monoallelic mutations in CC2D1A suggest a novel role in human heterotaxy and ciliary dysfunction","volume":"13","author":"Ma","year":"2020","journal-title":"Circ: Genomic Precis Med"},{"key":"10.1016\/j.gde.2022.101937_sbref47","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41588-021-00970-4","article-title":"Discovery of a genetic module essential for assigning left\u2013right asymmetry in humans and ancestral vertebrates","volume":"54","author":"Szenker-Ravi","year":"2021","journal-title":"Nat Genet"}],"container-title":["Current Opinion in Genetics &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959437X22000466?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959437X22000466?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T12:05:14Z","timestamp":1760702714000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0959437X22000466"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":47,"alternative-id":["S0959437X22000466"],"URL":"https:\/\/doi.org\/10.1016\/j.gde.2022.101937","relation":{},"ISSN":["0959-437X"],"issn-type":[{"value":"0959-437X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The genetic landscape of cardiovascular left\u2013right patterning defects","name":"articletitle","label":"Article Title"},{"value":"Current Opinion in Genetics & Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.gde.2022.101937","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"101937"}}