{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:08:43Z","timestamp":1789754923386,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1010236","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL 109758"],"award-info":[{"award-number":["R01 HL 109758"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007520","name":"Nationwide Children's Hospital","doi-asserted-by":"publisher","award":["Nationwide Children's Hospital Foundation"],"award-info":[{"award-number":["Nationwide Children's Hospital Foundation"]}],"id":[{"id":"10.13039\/100007520","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007520","name":"Nationwide Children's Hospital","doi-asserted-by":"publisher","award":["Nationwide Foundation Pediatric Innovation"],"award-info":[{"award-number":["Nationwide Foundation Pediatric Innovation"]}],"id":[{"id":"10.13039\/100007520","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5U54HG006542"],"award-info":[{"award-number":["5U54HG006542"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Congenital heart disease (CHD) is a common group of birth defects with a strong genetic contribution to their etiology, but historically the diagnostic yield from exome studies of isolated CHD has been low. Pleiotropy, variable expressivity, and the difficulty of accurately phenotyping newborns contribute to this problem. We hypothesized that performing exome sequencing on selected individuals in families with multiple members affected by left-sided CHD, then filtering variants by population frequency,<jats:italic>in silico<\/jats:italic>predictive algorithms, and phenotypic annotations from publicly available databases would increase this yield and generate a list of candidate disease-causing variants that would show a high validation rate. In eight of the nineteen families in our study (42%), we established a well-known gene\/phenotype link for a candidate variant or performed confirmation of a candidate variant\u2019s effect on protein function, including variants in genes not previously described or firmly established as disease genes in the body of CHD literature:<jats:italic>BMP10<\/jats:italic>,<jats:italic>CASZ1<\/jats:italic>,<jats:italic>ROCK1<\/jats:italic>and<jats:italic>SMYD1<\/jats:italic>. Two plausible variants in different genes were found to segregate in the same family in two instances suggesting oligogenic inheritance. These results highlight the need for functional validation and demonstrate that in the era of next-generation sequencing, multiplex families with isolated CHD can still bring high yield to the discovery of novel disease genes.<\/jats:p>","DOI":"10.1371\/journal.pgen.1010236","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T17:49:09Z","timestamp":1656006549000},"page":"e1010236","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Exome sequencing in multiplex families with left-sided cardiac defects has high yield for disease gene discovery"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7307-6274","authenticated-orcid":true,"given":"David M.","family":"Gordon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Cunningham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Zender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0665-418X","authenticated-orcid":true,"given":"Patrick J.","family":"Lawrence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0056-5434","authenticated-orcid":true,"given":"Jacqueline S.","family":"Penaloza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2316-2486","authenticated-orcid":true,"given":"Sara M.","family":"Fitzgerald-Butt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1963-935X","authenticated-orcid":true,"given":"Katherine","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Duong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J.","family":"Corsmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1762-9414","authenticated-orcid":true,"given":"Jeffrey B.","family":"Gaither","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4755-6869","authenticated-orcid":true,"given":"Harkness C.","family":"Kuck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saranga","family":"Wijeratne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7536-9537","authenticated-orcid":true,"given":"Blythe","family":"Moreland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7796-3994","authenticated-orcid":true,"given":"Benjamin J.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Baylor-Johns Hopkins Center for Mendelian Genomics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3778-5927","authenticated-orcid":true,"given":"Vidu","family":"Garg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-5903","authenticated-orcid":true,"given":"Peter","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8407-8942","authenticated-orcid":true,"given":"Kim L.","family":"McBride","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"issue":"12","key":"pgen.1010236.ref001","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1016\/S0735-1097(02)01886-7","article-title":"The incidence of congenital heart disease","volume":"39","author":"JI Hoffman","year":"2002","journal-title":"Journal of the American College of Cardiology"},{"issue":"21","key":"pgen.1010236.ref002","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1016\/j.jacc.2011.08.025","article-title":"Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis","volume":"58","author":"D van der Linde","year":"2011","journal-title":"Journal of the American College of Cardiology"},{"issue":"16","key":"pgen.1010236.ref003","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1016\/j.jacc.2007.07.021","article-title":"Hypoplastic left heart syndrome is heritable","volume":"50","author":"RB Hinton","year":"2007","journal-title":"Journal of the American College of Cardiology"},{"issue":"8","key":"pgen.1010236.ref004","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/bdra.20169","article-title":"Epidemiology of noncomplex left ventricular outflow tract obstruction malformations (aortic valve stenosis, coarctation of the aorta, hypoplastic left heart syndrome) in Texas, 1999\u20132001.","volume":"73","author":"KL McBride","year":"2005","journal-title":"Birth defects research Part A, Clinical and molecular teratology"},{"issue":"2","key":"pgen.1010236.ref005","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/ajmg.a.30602","article-title":"Inheritance analysis of congenital left ventricular outflow tract obstruction malformations: Segregation, multiplex relative risk, and heritability","volume":"134A","author":"KL McBride","year":"2005","journal-title":"Am J Med Genet A"},{"issue":"21","key":"pgen.1010236.ref006","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":"ME Pierpont","year":"2018","journal-title":"Circulation"},{"issue":"6947","key":"pgen.1010236.ref007","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature01827","article-title":"GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5","volume":"424","author":"V Garg","year":"2003","journal-title":"Nature"},{"issue":"7056","key":"pgen.1010236.ref008","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nature03940","article-title":"Mutations in NOTCH1 cause aortic valve disease","volume":"437","author":"V Garg","year":"2005","journal-title":"Nature"},{"issue":"4","key":"pgen.1010236.ref009","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/ng1526","article-title":"Mutation in myosin heavy chain 6 causes atrial septal defect","volume":"37","author":"YH Ching","year":"2005","journal-title":"Nat Genet"},{"issue":"2","key":"pgen.1010236.ref010","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/hmg\/ddm302","article-title":"Alpha-cardiac actin mutations produce atrial septal defects","volume":"17","author":"H Matsson","year":"2008","journal-title":"Hum Mol Genet"},{"issue":"5373","key":"pgen.1010236.ref011","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1126\/science.281.5373.108","article-title":"Congenital heart disease caused by mutations in the transcription factor NKX2-5","volume":"281","author":"JJ Schott","year":"1998","journal-title":"Science"},{"issue":"4","key":"pgen.1010236.ref012","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1161\/CIRCRESAHA.111.300297","article-title":"The Congenital Heart Disease Genetic Network Study: rationale, design, and early results","volume":"112","author":"C Pediatric Cardiac Genomics","year":"2013","journal-title":"Circ Res"},{"issue":"7453","key":"pgen.1010236.ref013","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nature12141","article-title":"De novo mutations in histone-modifying genes in congenital heart disease","volume":"498","author":"S Zaidi","year":"2013","journal-title":"Nature"},{"issue":"11","key":"pgen.1010236.ref014","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1038\/ng.3970","article-title":"Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands","volume":"49","author":"SC Jin","year":"2017","journal-title":"Nat Genet"},{"issue":"6265","key":"pgen.1010236.ref015","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1126\/science.aac9396","article-title":"De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies","volume":"350","author":"J Homsy","year":"2015","journal-title":"Science"},{"issue":"9","key":"pgen.1010236.ref016","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/ng.3627","article-title":"Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing","volume":"48","author":"A Sifrim","year":"2016","journal-title":"Nat Genet"},{"issue":"6","key":"pgen.1010236.ref017","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"AR Quinlan","year":"2010","journal-title":"Bioinformatics"},{"issue":"8","key":"pgen.1010236.ref018","doi-asserted-by":"crossref","first-page":"e828","DOI":"10.1002\/mgg3.828","article-title":"A novel de novo CASZ1 heterozygous frameshift variant causes dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy","volume":"7","author":"J Guo","year":"2019","journal-title":"Mol Genet Genomic Med"},{"issue":"1","key":"pgen.1010236.ref019","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.gene.2016.09.044","article-title":"CASZ1 loss-of-function mutation associated with congenital heart disease","volume":"595","author":"RT Huang","year":"2016","journal-title":"Gene"},{"issue":"9","key":"pgen.1010236.ref020","first-page":"1417","article-title":"CASZ1 loss-of-function mutation contributes to familial dilated cardiomyopathy","volume":"55","author":"XB Qiu","year":"2017","journal-title":"Clin Chem Lab Med"},{"issue":"11","key":"pgen.1010236.ref021","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1242\/dev.119107","article-title":"Casz1 is required for cardiomyocyte G1-to-S phase progression during mammalian cardiac development","volume":"142","author":"KM Dorr","year":"2015","journal-title":"Development"},{"issue":"43","key":"pgen.1010236.ref022","doi-asserted-by":"crossref","first-page":"29801","DOI":"10.1074\/jbc.M114.570416","article-title":"Essential role of the zinc finger transcription factor Casz1 for mammalian cardiac morphogenesis and development","volume":"289","author":"Z Liu","year":"2014","journal-title":"J Biol Chem"},{"issue":"1","key":"pgen.1010236.ref023","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13073-017-0482-5","article-title":"Whole exome sequencing in 342 congenital cardiac left sided lesion cases reveals extensive genetic heterogeneity and complex inheritance patterns","volume":"9","author":"AH Li","year":"2017","journal-title":"Genome Med"},{"issue":"3","key":"pgen.1010236.ref024","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/cvr\/cvt132","article-title":"Neural crest cells are required for correct positioning of the developing outflow cushions and pattern the arterial valve leaflets","volume":"99","author":"HM Phillips","year":"2013","journal-title":"Cardiovasc Res"},{"issue":"21","key":"pgen.1010236.ref025","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.1093\/hmg\/ddt283","article-title":"MCTP2 is a dosage-sensitive gene required for cardiac outflow tract development","volume":"22","author":"SR Lalani","year":"2013","journal-title":"Hum Mol Genet"},{"issue":"1","key":"pgen.1010236.ref026","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41588-018-0265-y","article-title":"ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm","volume":"51","author":"RA Gould","year":"2019","journal-title":"Nat Genet"},{"issue":"15","key":"pgen.1010236.ref027","doi-asserted-by":"crossref","first-page":"5296","DOI":"10.1128\/MCB.22.15.5296-5307.2002","article-title":"Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development","volume":"22","author":"JD Hildebrand","year":"2002","journal-title":"Mol Cell Biol"},{"issue":"1","key":"pgen.1010236.ref028","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/ng866","article-title":"Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis","volume":"31","author":"PD Gottlieb","year":"2002","journal-title":"Nat Genet"},{"issue":"9","key":"pgen.1010236.ref029","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1242\/dev.01094","article-title":"BMP10 is essential for maintaining cardiac growth during murine cardiogenesis","volume":"131","author":"H Chen","year":"2004","journal-title":"Development"},{"issue":"4","key":"pgen.1010236.ref030","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1161\/CIRCGENETICS.115.001070","article-title":"Recessive MYH6 Mutations in Hypoplastic Left Heart With Reduced Ejection Fraction.","volume":"8","author":"JL Theis","year":"2015","journal-title":"Circ Cardiovasc Genet"},{"issue":"12","key":"pgen.1010236.ref031","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":"H Liu","year":"2020","journal-title":"Hum Mutat"},{"issue":"8","key":"pgen.1010236.ref032","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1093\/hmg\/ddv004","article-title":"MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus","volume":"24","author":"F Quintero-Rivera","year":"2015","journal-title":"Hum Mol Genet"},{"issue":"18","key":"pgen.1010236.ref033","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1093\/hmg\/ddn187","article-title":"NOTCH1 mutations in individuals with left ventricular outflow tract malformations reduce ligand-induced signaling","volume":"17","author":"KL McBride","year":"2008","journal-title":"Hum Mol Genet"},{"issue":"9","key":"pgen.1010236.ref034","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/gim.2015.193","article-title":"Cardiovascular malformations caused by NOTCH1 mutations do not keep left: data on 428 probands with left-sided CHD and their families","volume":"18","author":"WS Kerstjens-Frederikse","year":"2016","journal-title":"Genet Med"},{"issue":"6","key":"pgen.1010236.ref035","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1161\/01.RES.0000260913.95642.3b","article-title":"Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition","volume":"100","author":"A Fischer","year":"2007","journal-title":"Circ Res"},{"issue":"9","key":"pgen.1010236.ref036","doi-asserted-by":"crossref","first-page":"e1007011","DOI":"10.1371\/journal.pgen.1007011","article-title":"Formation of a TBX20-CASZ1 protein complex is protective against dilated cardiomyopathy and critical for cardiac homeostasis","volume":"13","author":"L Kennedy","year":"2017","journal-title":"PLoS genetics"},{"key":"pgen.1010236.ref037","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.matbio.2018.02.021","article-title":"Elastin-driven genetic diseases","volume":"71\u201372","author":"ML Duque Lasio","year":"2018","journal-title":"Matrix Biol"},{"issue":"9","key":"pgen.1010236.ref038","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1093\/hmg\/4.9.1677","article-title":"A 30 kb deletion within the elastin gene results in familial supravalvular aortic stenosis","volume":"4","author":"TM Olson","year":"1995","journal-title":"Hum Mol Genet"},{"issue":"3","key":"pgen.1010236.ref039","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.matbio.2012.01.001","article-title":"Maladaptive matrix remodeling and regional biomechanical dysfunction in a mouse model of aortic valve disease","volume":"31","author":"VK Krishnamurthy","year":"2012","journal-title":"Matrix Biol"},{"issue":"1","key":"pgen.1010236.ref040","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/s41467-020-14684-4","article-title":"CASZ1 induces skeletal muscle and rhabdomyosarcoma differentiation through a feed-forward loop with MYOD and MYOG.","volume":"11","author":"Z Liu","year":"2020","journal-title":"Nature communications"},{"issue":"1","key":"pgen.1010236.ref041","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/onc.2016.179","article-title":"Identification of CASZ1 NES reveals potential mechanisms for loss of CASZ1 tumor suppressor activity in neuroblastoma","volume":"36","author":"Z Liu","year":"2017","journal-title":"Oncogene"},{"key":"pgen.1010236.ref042","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2009.06.086","article-title":"Functional consequences of genetic variation in primates on tyrosine hydroxylase (TH) expression in vitro","volume":"1288","author":"LR Warner","year":"2009","journal-title":"Brain Res"},{"issue":"6","key":"pgen.1010236.ref043","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1083\/jcb.200411179","article-title":"ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles","volume":"168","author":"Y Shimizu","year":"2005","journal-title":"J Cell Biol"},{"issue":"7","key":"pgen.1010236.ref044","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/s41580-019-0126-2","article-title":"Quality and quantity control of gene expression by nonsense-mediated mRNA decay","volume":"20","author":"T Kurosaki","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pgen.1010236.ref045","doi-asserted-by":"crossref","first-page":"144371","DOI":"10.1016\/j.gene.2020.144371","article-title":"Temporal and spatial expression of zebrafish mctp genes and evaluation of frameshift alleles of mctp2b","volume":"738","author":"AE Espino-Saldana","year":"2020","journal-title":"Gene"},{"issue":"8","key":"pgen.1010236.ref046","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s00439-017-1821-8","article-title":"The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes","volume":"136","author":"D Monies","year":"2017","journal-title":"Hum Genet"},{"issue":"48","key":"pgen.1010236.ref047","doi-asserted-by":"crossref","first-page":"20750","DOI":"10.1073\/pnas.1013493107","article-title":"skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration","volume":"107","author":"CY Park","year":"2010","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"3","key":"pgen.1010236.ref048","doi-asserted-by":"crossref","first-page":"e0121765","DOI":"10.1371\/journal.pone.0121765","article-title":"Smyd1 facilitates heart development by antagonizing oxidative and ER stress responses","volume":"10","author":"TL Rasmussen","year":"2015","journal-title":"PloS one"},{"issue":"2","key":"pgen.1010236.ref049","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0925-4773(98)00221-4","article-title":"Heart specific expression of mouse BMP-10 a novel member of the TGF-beta superfamily","volume":"80","author":"H Neuhaus","year":"1999","journal-title":"Mech Dev"},{"issue":"26","key":"pgen.1010236.ref050","doi-asserted-by":"crossref","first-page":"22785","DOI":"10.1074\/jbc.M111.233577","article-title":"Furin is the major processing enzyme of the cardiac-specific growth factor bone morphogenetic protein 10","volume":"286","author":"D Susan-Resiga","year":"2011","journal-title":"J Biol Chem"},{"key":"pgen.1010236.ref051","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/B978-0-12-405943-6.00008-7","article-title":"Hey bHLH transcription factors","volume":"110","author":"D Weber","year":"2014","journal-title":"Curr Top Dev Biol"},{"issue":"5","key":"pgen.1010236.ref052","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1161\/01.RES.0000141136.85194.f0","article-title":"Targeted disruption of hesr2 results in atrioventricular valve anomalies that lead to heart dysfunction","volume":"95","author":"H Kokubo","year":"2004","journal-title":"Circ Res"},{"issue":"12","key":"pgen.1010236.ref053","first-page":"1492","article-title":"Cardiac malformations in relatives of infants with hypoplastic left-heart syndrome","volume":"143","author":"JI Brenner","year":"1989","journal-title":"American journal of diseases of children (1960)."},{"issue":"12","key":"pgen.1010236.ref054","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.jacc.2008.12.023","article-title":"Hypoplastic left heart syndrome links to chromosomes 10q and 6q and is genetically related to bicuspid aortic valve","volume":"53","author":"RB Hinton","year":"2009","journal-title":"Journal of the American College of Cardiology"},{"issue":"11","key":"pgen.1010236.ref055","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1016\/j.amjcard.2015.08.045","article-title":"Familial Incidence of Cardiovascular Malformations in Hypoplastic Left Heart Syndrome.","volume":"116","author":"AM Kelle","year":"2015","journal-title":"The American journal of cardiology"},{"issue":"3","key":"pgen.1010236.ref056","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1542\/peds.2003-0782-L","article-title":"Echocardiographic evaluation of asymptomatic parental and sibling cardiovascular anomalies associated with congenital left ventricular outflow tract lesions","volume":"114","author":"MB Lewin","year":"2004","journal-title":"Pediatrics"},{"issue":"4","key":"pgen.1010236.ref057","doi-asserted-by":"crossref","first-page":"e18557","DOI":"10.1371\/journal.pone.0018557","article-title":"CASZ1b, the short isoform of CASZ1 gene, coexpresses with CASZ1a during neurogenesis and suppresses neuroblastoma cell growth","volume":"6","author":"Z Liu","year":"2011","journal-title":"PloS one."},{"issue":"34","key":"pgen.1010236.ref058","first-page":"E7987","article-title":"Casz1 controls higher-order nuclear organization in rod photoreceptors","volume":"115","author":"P Mattar","year":"2018","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"3","key":"pgen.1010236.ref059","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1046\/j.1365-2443.1998.00181.x","article-title":"Myosin II activation promotes neurite retraction during the action of Rho and Rho-kinase","volume":"3","author":"M Amano","year":"1998","journal-title":"Genes Cells"},{"issue":"39","key":"pgen.1010236.ref060","doi-asserted-by":"crossref","first-page":"14495","DOI":"10.1073\/pnas.0601911103","article-title":"Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis.","volume":"103","author":"J Chang","year":"2006","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"8","key":"pgen.1010236.ref061","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.125172","article-title":"Disruption of embryonic ROCK signaling reproduces the sarcomeric phenotype of hypertrophic cardiomyopathy.","volume":"5","author":"KE Bailey","year":"2019","journal-title":"JCI Insight"},{"issue":"22","key":"pgen.1010236.ref062","doi-asserted-by":"crossref","first-page":"4434","DOI":"10.1128\/MCB.00577-13","article-title":"Noncanonical NOTCH signaling limits self-renewal of human epithelial and induced pluripotent stem cells through ROCK activation","volume":"33","author":"T Yugawa","year":"2013","journal-title":"Mol Cell Biol"},{"issue":"1","key":"pgen.1010236.ref063","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.bbadis.2010.10.002","article-title":"NOTCH1 missense alleles associated with left ventricular outflow tract defects exhibit impaired receptor processing and defective EMT","volume":"1812","author":"MF Riley","year":"2011","journal-title":"Biochimica et biophysica acta"},{"issue":"2","key":"pgen.1010236.ref064","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1002\/dvdy.23717","article-title":"Notch pathway regulation of neural crest cell development in vivo","volume":"241","author":"TJ Mead","year":"2012","journal-title":"Dev Dyn"},{"issue":"11","key":"pgen.1010236.ref065","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1242\/dev.01849","article-title":"BOP, a regulator of right ventricular heart development, is a direct transcriptional target of MEF2C in the developing heart","volume":"132","author":"D Phan","year":"2005","journal-title":"Development"},{"key":"pgen.1010236.ref066","first-page":"9","article-title":"GATA6 mutations in hiPSCs inform mechanisms for maldevelopment of the heart, pancreas, and diaphragm","author":"A Sharma","year":"2020","journal-title":"Elife"},{"issue":"12","key":"pgen.1010236.ref067","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1016\/j.amjcard.2014.09.028","article-title":"A novel NKX2.5 loss-of-function mutation associated with congenital bicuspid aortic valve","volume":"114","author":"XK Qu","year":"2014","journal-title":"The American journal of cardiology"},{"issue":"10","key":"pgen.1010236.ref068","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.1172\/JCI63635","article-title":"Myocardin regulates BMP10 expression and is required for heart development","volume":"122","author":"J Huang","year":"2012","journal-title":"J Clin Invest"},{"issue":"4","key":"pgen.1010236.ref069","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1161\/CIRCGENETICS.115.001324","article-title":"Utilization of Whole Exome Sequencing to Identify Causative Mutations in Familial Congenital Heart Disease.","volume":"9","author":"S LaHaye","year":"2016","journal-title":"Circ Cardiovasc Genet"},{"issue":"7","key":"pgen.1010236.ref070","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/ng.3870","article-title":"The complex genetics of hypoplastic left heart syndrome","volume":"49","author":"X Liu","year":"2017","journal-title":"Nat Genet"},{"issue":"1","key":"pgen.1010236.ref071","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13059-014-0577-x","article-title":"Churchill: an ultra-fast, deterministic, highly scalable and balanced parallelization strategy for the discovery of human genetic variation in clinical and population-scale genomics","volume":"16","author":"BJ Kelly","year":"2015","journal-title":"Genome Biol"},{"issue":"1110","key":"pgen.1010236.ref072","first-page":"11.0.1","article-title":"From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline","volume":"43","author":"GA Van der Auwera","year":"2013","journal-title":"Curr Protoc Bioinformatics"},{"issue":"2","key":"pgen.1010236.ref073","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3.","volume":"6","author":"P Cingolani","year":"2012","journal-title":"Fly (Austin)."},{"issue":"7809","key":"pgen.1010236.ref074","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"KJ Karczewski","year":"2020","journal-title":"Nature"},{"issue":"3","key":"pgen.1010236.ref075","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"M Kircher","year":"2014","journal-title":"Nat Genet"},{"issue":"3","key":"pgen.1010236.ref076","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/humu.22932","article-title":"dbNSFP v3.0: A One-Stop Database of Functional Predictions and Annotations for Human Nonsynonymous and Splice-Site SNVs","volume":"37","author":"X Liu","year":"2016","journal-title":"Hum Mutat"},{"issue":"23","key":"pgen.1010236.ref077","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1016\/j.jacc.2014.09.048","article-title":"Targeted next-generation sequencing identifies pathogenic variants in familial congenital heart disease","volume":"64","author":"GM Blue","year":"2014","journal-title":"J Am Coll Cardiol"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1010236","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1010236","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T17:18:48Z","timestamp":1700759928000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1010236"}},"subtitle":[],"editor":[{"given":"Anne","family":"O\u2019Donnell-Luria","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,6,23]]},"references-count":77,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1010236","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pgen.1010236","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,23]]}}}