{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:48:48Z","timestamp":1790768928494,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101685"],"award-info":[{"award-number":["82101685"]}],"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":["82171599"],"award-info":[{"award-number":["82171599"]}],"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":["81971333"],"award-info":[{"award-number":["81971333"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"2020 Basic and Clinical Cooperative Research Promotion Program of Anhui Medical University","award":["2020xkjT014"],"award-info":[{"award-number":["2020xkjT014"]}]},{"name":"Anhui Provincial Undergraduate Innovation and Entrepreneurship Training Program","award":["S202010366092"],"award-info":[{"award-number":["S202010366092"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Several different mutations in the proteome of centriole 1 centriolar protein B (POC1B) have been linked to cone dystrophy or cone-rod dystrophy (CORD). However, mutations in POC1B that are associated with both CORD and oligoasthenoteratozoospermia (OAT) have not been reported previously. Here, whole-exome sequencing was performed to identify a homozygous frameshift variant (c.151delG) in POC1B in the two brothers who had been diagnosed with both CORD and OAT from a consanguineous family. Transcript and protein analyses of biological samples from the two patients carrying the variant showed that POC1B protein is lost in sperm cells. The system CRISPR\/Cas9 was utilized to create poc1bc.151delG\/c.151delG knock-in (KI) mice. Notably, poc1bc.151delG\/c.151delG KI male mice presented with OAT phenotype. Additionally, testicular histology and transmission electron microscopy analysis of the testes and sperm indicated that Poc1b mutation results in abnormal formation of acrosomes and flagella. Collectively, according to our experimental data on human volunteers and animal models, biallelic mutations in POC1B can cause OAT and CORD in mice and humans.<\/jats:p>","DOI":"10.1093\/hmg\/ddad061","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T11:59:41Z","timestamp":1681819181000},"page":"2307-2317","source":"Crossref","is-referenced-by-count":17,"title":["Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice"],"prefix":"10.1093","volume":"32","author":[{"given":"Juan","family":"Hua","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology , School of Basic Medical Sciences, , Hefei 230032 , China"},{"name":"Anhui Medical University , School of Basic Medical Sciences, , Hefei 230032 , China"},{"name":"Translational Medicine Research Center, The Second Affiliated Hospital of Anhui Medical University , Hefei 230032 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xu","sequence":"additional","affiliation":[{"name":"Reproductive and Genetic Hospital , The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, , Hefei 230001 , China"},{"name":"University of Science and Technology of China , The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, , Hefei 230001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology , School of Basic Medical Sciences, , Hefei 230032 , China"},{"name":"Anhui Medical University , School of Basic Medical Sciences, , Hefei 230032 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JingTian","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology , School of Basic Medical Sciences, , Hefei 230032 , China"},{"name":"Anhui Medical University , School of Basic Medical Sciences, , Hefei 230032 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking University First Hospital , Beijing 100034 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoJun","family":"Zha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology , School of Basic Medical Sciences, , Hefei 230032 , China"},{"name":"Anhui Medical University , School of Basic Medical Sciences, , Hefei 230032 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiansheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Anhui Medical University , Hefei 230022 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Wan","sequence":"additional","affiliation":[{"name":"Reproductive and Genetic Hospital , The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, , Hefei 230001 , China"},{"name":"University of Science and Technology of China , The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, , Hefei 230001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"2023070515080346000_ref1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1111\/andr.12062","article-title":"Expression profiles of NPHP1 in the germ cells in the semen of men with male factor infertility","volume":"3","author":"Devi","year":"2015","journal-title":"Andrology"},{"key":"2023070515080346000_ref2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3389\/fcell.2019.00188","article-title":"The role of sperm centrioles in human reproduction - the known and the unknown","volume":"7","author":"Avidor-Reiss","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"2023070515080346000_ref3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00439-019-01974-1","article-title":"New insights into the genetics of spermatogenic failure: a review of the literature","volume":"138","author":"Cannarella","year":"2019","journal-title":"Hum. Genet."},{"key":"2023070515080346000_ref4","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1262\/jrd.2021-063","article-title":"The I510V mutation in KLHL10 in a patient with oligoasthenoteratozoospermia","volume":"67","author":"Huang","year":"2021","journal-title":"J Reprod. Dev."},{"key":"2023070515080346000_ref5","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/andr.12077","article-title":"Treatment strategies for severe oligoasthenoteratozoospermia (OAT) (&lt;0.1 million\/mL) patients","volume":"3","author":"Nordhoff","year":"2015","journal-title":"Andrology"},{"key":"2023070515080346000_ref6","doi-asserted-by":"crossref","DOI":"10.1111\/and.13586","article-title":"Role of genetics and epigenetics in male infertility","volume":"53","author":"Gunes","year":"2021","journal-title":"Andrologia"},{"key":"2023070515080346000_ref7","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1093\/hmg\/ddab171","article-title":"Loss of DRC1 function leads to multiple morphological abnormalities of the sperm flagella and male infertility in human and mouse","volume":"30","author":"Zhang","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"2023070515080346000_ref8","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.ajhg.2009.03.004","article-title":"Human male infertility caused by mutations in the CATSPER1 channel protein","volume":"84","author":"Avenarius","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"2023070515080346000_ref9","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/sj.ejhg.5200991","article-title":"CATSPER2, a human autosomal nonsyndromic male infertility gene","volume":"11","author":"Avidan","year":"2003","journal-title":"Eur. J Hum. Genet."},{"key":"2023070515080346000_ref10","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/mrd.23310","article-title":"Single-nucleotide polymorphism c.474G&gt;a in the SEPT12 gene is a predisposing factor in male infertility","volume":"87","author":"Rafaee","year":"2020","journal-title":"Mol. Reprod. Dev."},{"key":"2023070515080346000_ref11","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.ajhg.2013.03.016","article-title":"Missense mutations in SLC26A8, encoding a sperm-specific activator of CFTR, are associated with human asthenozoospermia","volume":"92","author":"Dirami","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"2023070515080346000_ref12","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1136\/jmedgenet-2013-102102","article-title":"Truncating mutations in TAF4B and ZMYND15 causing recessive azoospermia","volume":"51","author":"Ayhan","year":"2014","journal-title":"J. Med. Genet."},{"key":"2023070515080346000_ref13","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1159\/000468934","article-title":"Two novel TEX15 mutations in a family with nonobstructive azoospermia","volume":"82","author":"Colombo","year":"2017","journal-title":"Gynecol. Obstet. Investig."},{"key":"2023070515080346000_ref14","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s10815-017-0900-z","article-title":"A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family","volume":"34","author":"Okutman","year":"2017","journal-title":"J. Assist. Reprod. Genet."},{"key":"2023070515080346000_ref15","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1136\/jmedgenet-2017-104514","article-title":"Mutation in TDRD9 causes non-obstructive azoospermia in infertile men","volume":"54","author":"Arafat","year":"2017","journal-title":"J. Med. Genet."},{"key":"2023070515080346000_ref16","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.gene.2017.10.014","article-title":"A novel mutation in HAUS7 results in severe oligozoospermia in two brothers","volume":"639","author":"Li","year":"2018","journal-title":"Gene"},{"key":"2023070515080346000_ref17","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s10815-016-0863-5","article-title":"The impact of RABL2B gene (rs144944885) on human male infertility in patients with oligoasthenoteratozoospermia and immotile short tail sperm defects","volume":"34","author":"Hosseini","year":"2017","journal-title":"J. Assist. Reprod. Genet."},{"key":"2023070515080346000_ref18","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1002\/humu.23993","article-title":"Functional characterization of the first missense variant in CEP78, a founder allele associated with cone-rod dystrophy, hearing loss, and reduced male fertility","volume":"41","author":"Ascari","year":"2020","journal-title":"Hum. Mutat."},{"key":"2023070515080346000_ref19","first-page":"4546","article-title":"Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility","volume":"25","author":"Bedoni","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"2023070515080346000_ref20","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1136\/jmedgenet-2021-107919","article-title":"Homozygous mutations in CCDC34 cause male infertility with oligoasthenoteratozoospermia in humans and mice","volume":"59","author":"Cong","year":"2022","journal-title":"J. Med. Genet."},{"key":"2023070515080346000_ref21","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1093\/hmg\/ddab185","article-title":"CFAP65 is required in the acrosome biogenesis and mitochondrial sheath assembly during spermiogenesis","volume":"30","author":"Wang","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"2023070515080346000_ref22","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/cge.13662","article-title":"Loss-of-function mutations in centrosomal protein 112 is associated with human acephalic spermatozoa phenotype","volume":"97","author":"Sha","year":"2020","journal-title":"Clin. Genet."},{"key":"2023070515080346000_ref23","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1242\/jcs.111203","article-title":"Poc1A and Poc1B act together in human cells to ensure centriole integrity","volume":"126","author":"Venoux","year":"2013","journal-title":"J. Cell Sci."},{"key":"2023070515080346000_ref24","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1083\/jcb.200908019","article-title":"Basal body stability and ciliogenesis requires the conserved component Poc1","volume":"187","author":"Pearson","year":"2009","journal-title":"J. Cell Biol."},{"key":"2023070515080346000_ref25","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1001\/jamaophthalmol.2014.1658","article-title":"Novel recessive cone-rod dystrophy caused by POC1B mutation","volume":"132","author":"Durlu","year":"2014","journal-title":"JAMA Ophthalmol."},{"key":"2023070515080346000_ref26","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1080\/13816810.2018.1430239","article-title":"Novel compound heterozygous mutation in the POC1B gene underlie peripheral cone dystrophy in a Chinese family","volume":"39","author":"Jin","year":"2018","journal-title":"Ophthalmic Genet."},{"key":"2023070515080346000_ref27","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1080\/13816810.2017.1408846","article-title":"Case of cone dystrophy with normal fundus appearance associated with biallelic POC1B variants","volume":"39","author":"Kominami","year":"2018","journal-title":"Ophthalmic Genet."},{"key":"2023070515080346000_ref28","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ajhg.2014.06.012","article-title":"Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy","volume":"95","author":"Roosing","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"2023070515080346000_ref29","doi-asserted-by":"crossref","DOI":"10.1210\/clinem\/dgaa551","article-title":"Reproduction function in male patients with Bardet Biedl syndrome","volume":"105","author":"Koscinski","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023070515080346000_ref30","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/gim.2017.130","article-title":"Loss-of-function mutations in TDRD7 lead to a rare novel syndrome combining congenital cataract and nonobstructive azoospermia in humans","volume":"21","author":"Tan","year":"2019","journal-title":"Genet. Med."},{"key":"2023070515080346000_ref31","doi-asserted-by":"crossref","first-page":"eabn0968","DOI":"10.1126\/sciadv.abn0968","article-title":"Loss-of-function mutations in CEP78 cause male infertility in humans and mice","volume":"8","author":"Zhang","year":"2022","journal-title":"Sci. Adv."},{"key":"2023070515080346000_ref32","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1080\/13816810.2021.1894460","article-title":"A homozygous POC1B variant causes recessive cone-rod dystrophy","volume":"42","author":"Peturson","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"2023070515080346000_ref33","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.bbrc.2015.06.083","article-title":"Knockdown of poc1b causes abnormal photoreceptor sensory cilium and vision impairment in zebrafish","volume":"465","author":"Zhang","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023070515080346000_ref34","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1080\/13816810.2020.1744017","article-title":"Investigation of CEP290 genotype-phenotype correlations in a patient with retinitis pigmentosa, infertility, end-stage renal disease, and a novel mutation","volume":"41","author":"Williamson","year":"2020","journal-title":"Ophthalmic Genet."},{"key":"2023070515080346000_ref35","doi-asserted-by":"crossref","first-page":"4824","DOI":"10.1038\/s41598-018-22096-0","article-title":"Clinical and genetic characteristics of 251 consecutive patients with macular and cone\/cone-rod dystrophy","volume":"8","author":"Birtel","year":"2018","journal-title":"Sci. Rep."},{"key":"2023070515080346000_ref36","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1002\/humu.22618","article-title":"Mutation of POC1B in a severe syndromic retinal ciliopathy","volume":"35","author":"Beck","year":"2014","journal-title":"Hum. Mutat."},{"key":"2023070515080346000_ref37","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/s41419-021-03755-z","article-title":"Loss of CEP70 function affects acrosome biogenesis and flagella formation during spermiogenesis","volume":"12","author":"Liu","year":"2021","journal-title":"Cell Death Dis."},{"key":"2023070515080346000_ref38","article-title":"CEP250 is required for maintaining centrosome cohesion in the germline and fertility in male mice","volume":"9","author":"Floriot","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"2023070515080346000_ref39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1003928","article-title":"Acute versus chronic loss of mammalian Azi1\/Cep131 results in distinct ciliary phenotypes","volume":"9","author":"Hall","year":"2013","journal-title":"PLoS Genet."},{"key":"2023070515080346000_ref40","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1530\/REP-21-0042","article-title":"CEP164 is essential for efferent duct multiciliogenesis and male fertility","volume":"162","author":"Hoque","year":"2021","journal-title":"Reproduction"},{"key":"2023070515080346000_ref41","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1038\/s41467-022-29109-7","article-title":"CEP128 is involved in spermatogenesis in humans and mice","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat. Commun."},{"key":"2023070515080346000_ref42","first-page":"3204","article-title":"Germline deletion of Cetn1 causes infertility in male mice","volume":"126","author":"Avasthi","year":"2013","journal-title":"J. Cell Sci."},{"key":"2023070515080346000_ref43","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1038\/s41467-018-04678-8","article-title":"A novel atypical sperm centriole is functional during human fertilization","volume":"9","author":"Fishman","year":"2018","journal-title":"Nat. Commun."},{"key":"2023070515080346000_ref44","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1016\/j.cub.2016.07.006","article-title":"Centriole remodeling during spermiogenesis in Drosophila","volume":"26","author":"Khire","year":"2016","journal-title":"Curr. Biol."},{"key":"2023070515080346000_ref45","article-title":"Poc1B and Sas-6 function together during the atypical centriole formation in Drosophila melanogaster","volume":"8","author":"Jo","year":"2019","journal-title":"Cell"},{"key":"2023070515080346000_ref46","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1005569","article-title":"LINE-1 mediated insertion into Poc1a (protein of centriole 1 a) causes growth insufficiency and male infertility in mice","volume":"11","author":"Geister","year":"2015","journal-title":"PLoS Genet."},{"key":"2023070515080346000_ref47","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ajhg.2012.06.003","article-title":"Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis syndrome is caused by a POC1A mutation","volume":"91","author":"Sarig","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"2023070515080346000_ref48","doi-asserted-by":"crossref","first-page":"186","DOI":"10.4103\/aja202160","article-title":"MBOAT1 homozygous missense variant causes nonobstructive azoospermia","volume":"24","author":"Wan","year":"2022","journal-title":"Asian J. Androl."},{"key":"2023070515080346000_ref49","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s10815-018-1374-3","article-title":"Whole-exome sequencing identified a novel mutation of AURKC in a Chinese family with macrozoospermia","volume":"36","author":"Hua","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"2023070515080346000_ref50","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.xfre.2021.04.003","article-title":"Assessing the clinical value of the Kruger strict morphology criteria over the World Health Organization fourth edition criteria","volume":"2","author":"Wald","year":"2021","journal-title":"F&S Rep."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddad061\/50216470\/ddad061.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/32\/14\/2307\/50823233\/ddad061.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/32\/14\/2307\/50823233\/ddad061.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T19:29:09Z","timestamp":1688585349000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/32\/14\/2307\/7127671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,18]]},"references-count":50,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,4,18]]},"published-print":{"date-parts":[[2023,7,4]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddad061","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,7,15]]},"published":{"date-parts":[[2023,4,18]]}}}