{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:49:06Z","timestamp":1790768946132,"version":"4.1.0"},"reference-count":37,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"vor","delay-in-days":186,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31625015"],"award-info":[{"award-number":["31625015"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31521003"],"award-info":[{"award-number":["31521003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation of the Department of Science and Technology of Anhui Province","award":["2017070802D150"],"award-info":[{"award-number":["2017070802D150"]}]},{"name":"Foundation of the Education Department of Anhui Province","award":["KJ2016A370"],"award-info":[{"award-number":["KJ2016A370"]}]},{"name":"Shanghai Medical Center of Key Programs for\u00a0Female Reproductive Diseases","award":["2017ZZ01016"],"award-info":[{"award-number":["2017ZZ01016"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["2017SHZDZX01"],"award-info":[{"award-number":["2017SHZDZX01"]}]}],"content-domain":{"domain":["ajhg.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[2019,4]]},"DOI":"10.1016\/j.ajhg.2019.02.020","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T14:46:29Z","timestamp":1553784389000},"page":"738-748","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":134,"title":["Bi-allelic Mutations in TTC21A Induce Asthenoteratospermia in Humans and Mice"],"prefix":"10.1016","volume":"104","author":[{"given":"Wangjie","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenmin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoudha","family":"Zouari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxiong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zine-Eddine","family":"Kherraf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Coutton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingrong","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyan","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Arnoult","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre F.","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4556-8276","authenticated-orcid":false,"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajhg.2019.02.020_bib1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/humupd\/dmv016","article-title":"Infertility around the globe: New thinking on gender, reproductive technologies and global movements in the 21st century","volume":"21","author":"Inhorn","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"10.1016\/j.ajhg.2019.02.020_bib2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/humupd\/dmv020","article-title":"Teratozoospermia: Spotlight on the main genetic actors in the human","volume":"21","author":"Coutton","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"10.1016\/j.ajhg.2019.02.020_bib3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0070-2153(08)00802-8","article-title":"Intraflagellar transport (IFT) role in ciliary assembly, resorption and signalling","volume":"85","author":"Pedersen","year":"2008","journal-title":"Curr. Top. Dev. Biol."},{"key":"10.1016\/j.ajhg.2019.02.020_bib4","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1242\/jcs.117069","article-title":"Intraflagellar transport proteins cycle between the flagellum and its base","volume":"126","author":"Buisson","year":"2013","journal-title":"J.\u00a0Cell Sci."},{"key":"10.1016\/j.ajhg.2019.02.020_bib5","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1073\/pnas.94.9.4457","article-title":"Transport of a novel complex in the cytoplasmic matrix of Chlamydomonas flagella","volume":"94","author":"Piperno","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2019.02.020_bib6","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nrm3085","article-title":"Ciliogenesis: Building the cell\u2019s antenna","volume":"12","author":"Ishikawa","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.ajhg.2019.02.020_bib7","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/S0960-9822(01)00484-5","article-title":"Localization of intraflagellar transport protein IFT52 identifies basal body transitional fibers as the docking site for IFT particles","volume":"11","author":"Deane","year":"2001","journal-title":"Curr. Biol."},{"key":"10.1016\/j.ajhg.2019.02.020_bib8","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/cm.21427","article-title":"Intraflagellar transporter protein 140 (IFT140), a component of IFT-A complex, is essential for male fertility and spermiogenesis in mice","volume":"75","author":"Zhang","year":"2018","journal-title":"Cytoskeleton (Hoboken)"},{"key":"10.1016\/j.ajhg.2019.02.020_bib9","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.1091\/mbc.e16-05-0318","article-title":"Intraflagellar transport protein IFT20 is essential for male fertility and spermiogenesis in mice","volume":"27","author":"Zhang","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.ajhg.2019.02.020_bib10","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1093\/biolre\/iox029","article-title":"IFT25, an intraflagellar transporter protein dispensable for ciliogenesis in somatic cells, is essential for sperm flagella formation","volume":"96","author":"Liu","year":"2017","journal-title":"Biol. Reprod."},{"key":"10.1016\/j.ajhg.2019.02.020_bib11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ydbio.2017.09.023","article-title":"Intraflagellar transporter protein (IFT27), an IFT25 binding partner, is essential for male fertility and spermiogenesis in mice","volume":"432","author":"Zhang","year":"2017","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ajhg.2019.02.020_bib12","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1093\/humrep\/dei126","article-title":"Gene deletions in an infertile man with sperm fibrous sheath dysplasia","volume":"20","author":"Baccetti","year":"2005","journal-title":"Hum. Reprod."},{"key":"10.1016\/j.ajhg.2019.02.020_bib13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ajhg.2013.11.017","article-title":"Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella","volume":"94","author":"Ben Khelifa","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib14","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.ajhg.2017.04.012","article-title":"Biallelic mutations in CFAP43 and CFAP44 cause male infertility with multiple morphological abnormalities of the sperm flagella","volume":"100","author":"Tang","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib15","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/s41467-017-02792-7","article-title":"Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human","volume":"9","author":"Coutton","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2019.02.020_bib16","doi-asserted-by":"crossref","first-page":"e13151","DOI":"10.1111\/and.13151","article-title":"Patients with multiple morphological abnormalities of the sperm flagella harbouring CFAP44 or CFAP43 mutations have a good pregnancy outcome following intracytoplasmic sperm injection","volume":"51","author":"Sha","year":"2019","journal-title":"Andrologia"},{"key":"10.1016\/j.ajhg.2019.02.020_bib17","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1093\/hmg\/ddy034","article-title":"Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia","volume":"27","author":"Lor\u00e8s","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib18","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.ajhg.2018.03.007","article-title":"Absence of CFAP69 causes male infertility due to multiple morphological abnormalities of the flagella in human and mouse","volume":"102","author":"Dong","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib19","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1136\/jmedgenet-2018-105486","article-title":"Novel homozygous CFAP69 mutations in humans and mice cause severe asthenoteratospermia with multiple morphological abnormalities of the sperm flagella","volume":"56","author":"He","year":"2019","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib20","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.ajhg.2018.07.014","article-title":"A homozygous ancestral SVA-insertion-mediated deletion in WDR66 induces multiple morphological abnormalities of the sperm\u00a0flagellum and male infertility","volume":"103","author":"Kherraf","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib21","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ajhg.2018.07.013","article-title":"Loss of calmodulin- and radial-spoke-associated complex protein CFAP251 leads to immotile spermatozoa lacking mitochondria and infertility in men","volume":"103","author":"Auguste","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib22","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s10038-018-0520-1","article-title":"Biallelic mutations of CFAP251 cause sperm flagellar defects and human male infertility","volume":"64","author":"Li","year":"2019","journal-title":"J.\u00a0Hum. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib23","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1093\/humrep\/dey264","article-title":"Whole-exome sequencing identifies mutations in FSIP2 as a recurrent cause of multiple morphological abnormalities of the sperm flagella","volume":"33","author":"Martinez","year":"2018","journal-title":"Hum. Reprod."},{"key":"10.1016\/j.ajhg.2019.02.020_bib24","article-title":"Homozygous loss-of-function mutations in FSIP2 cause male infertility with asthenoteratospermia","volume":"46","author":"Liu","year":"2018","journal-title":"J.\u00a0Genet. Genomics"},{"key":"10.1016\/j.ajhg.2019.02.020_bib25","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ajhg.2018.12.013","article-title":"Bi-allelic mutations in ARMC2 lead to severe astheno-teratozoospermia due to sperm flagellum malformations in humans and mice","volume":"104","author":"Coutton","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib26","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41467-018-08182-x","article-title":"Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella","volume":"10","author":"Shen","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2019.02.020_bib27","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1083\/jcb.151.3.709","article-title":"Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella","volume":"151","author":"Pazour","year":"2000","journal-title":"J.\u00a0Cell Biol."},{"key":"10.1016\/j.ajhg.2019.02.020_bib28","doi-asserted-by":"crossref","first-page":"6943","DOI":"10.1073\/pnas.1221011110","article-title":"Evolution of modular intraflagellar transport from a coatomer-like progenitor","volume":"110","author":"van Dam","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2019.02.020_bib29","doi-asserted-by":"crossref","first-page":"513","DOI":"10.4103\/1008-682X.146100","article-title":"Morphological characteristics and initial genetic study of multiple morphological anomalies of the flagella in China","volume":"17","author":"Yang","year":"2015","journal-title":"Asian J. Androl."},{"key":"10.1016\/j.ajhg.2019.02.020_bib30","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"Ran","year":"2013","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.ajhg.2019.02.020_bib31","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/rmb2.12067","article-title":"Revolutionizing male fertility factor research in mice by using the genome editing tool CRISPR\/Cas9","volume":"17","author":"Abbasi","year":"2017","journal-title":"Reprod. Med. Biol."},{"key":"10.1016\/j.ajhg.2019.02.020_bib32","series-title":"The Centrosome: Cell and Molecular Mechanisms of Functions and Dysfunctions in Disease","first-page":"33","article-title":"Sperm Centrioles and Their Dual Role in Flagellogenesis and Cell Cycle of the Zygote","author":"Chemes","year":"2012"},{"key":"10.1016\/j.ajhg.2019.02.020_bib33","doi-asserted-by":"crossref","first-page":"E430","DOI":"10.1073\/pnas.1424648112","article-title":"Spata6 is required for normal assembly of the sperm connecting piece and tight head-tail conjunction","volume":"112","author":"Yuan","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2019.02.020_bib34","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/ng.105","article-title":"THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia","volume":"40","author":"Tran","year":"2008","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib35","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ng.756","article-title":"TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum","volume":"43","author":"Davis","year":"2011","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib36","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1146\/annurev.genom.7.080505.115610","article-title":"The ciliopathies: An emerging class of human genetic disorders","volume":"7","author":"Badano","year":"2006","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"10.1016\/j.ajhg.2019.02.020_bib37","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nrm2278","article-title":"When cilia go bad: Cilia defects and ciliopathies","volume":"8","author":"Fliegauf","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929719300655?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929719300655?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:02:13Z","timestamp":1694736133000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929719300655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["S0002929719300655"],"URL":"https:\/\/doi.org\/10.1016\/j.ajhg.2019.02.020","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2019,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Bi-allelic Mutations in TTC21A Induce Asthenoteratospermia in Humans and Mice","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Human Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajhg.2019.02.020","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 American Society of Human Genetics.","name":"copyright","label":"Copyright"}]}}