{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:38:20Z","timestamp":1792636700695,"version":"4.5.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019475","name":"Sidra Medicine","doi-asserted-by":"publisher","award":["SDR400185"],"award-info":[{"award-number":["SDR400185"]}],"id":[{"id":"10.13039\/100019475","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019475","name":"Sidra Medicine","doi-asserted-by":"publisher","award":["SDR400185"],"award-info":[{"award-number":["SDR400185"]}],"id":[{"id":"10.13039\/100019475","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>What are the genetic causes of asthenoteratozoospermia in consanguineous families, and what is the specific role of cilia- and flagella-associated proteins (CFAP) 46 in mammalian spermiogenesis?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>CFAP46 is a central apparatus protein essential for sperm flagellar assembly and head remodeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>Asthenoteratozoospermia is a genetically heterogeneous condition characterized by reduced sperm motility and abnormal morphology. While several CFAPs are known to support axonemal organization, the functional role of CFAP46 in mammals remained uncharacterized prior to this study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>We performed whole-genome or whole-exome sequencing on 13 consanguineous families affected by primary male infertility. Functional validation was conducted using three CRISPR\/Cas9-engineered mouse models: a null allele, a FLAG-tagged knock-in, and a humanized patient-specific nonsense allele.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>Genomic DNA from affected individuals and fertile relatives was analyzed by NGS and validated via Sanger sequencing. Mouse phenotypes were characterized through sperm analysis, immunofluorescence, and electron microscopy. Protein interactions were identified via immunoprecipitation and mass spectrometry. Additionally, a gene-level burden analysis was applied to unresolved cases across 345 spermiogenesis-associated genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>We identified homozygous loss-of-function variants in CFAP46, CFAP57, SEPTIN4, and SPEM2 segregating with infertility. Cfap46-deficient males were infertile due to significantly decreased sperm count, motility, and severe axonemal disruptions. CFAP46 was found to form an in vivo complex with CFAP54, CFAP74, and CFAP221. In families without a monogenic cause, affected individuals harbored a significantly higher burden of rare deleterious variants (4\u201316 genes) compared to fertile controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LARGE SCALE DATA<\/jats:title>\n                    <jats:p>Large-scale datasets and scripts are available via GitHub (https:\/\/github.com\/sirusb\/Nawaz_et_al_scripts).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>While functional mouse data strongly supports the identified variants, the rare-variant burden analysis identifies associations that require further functional validation to confirm specific oligogenic interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>This study establishes CFAP46 as a regulator of mammalian spermiogenesis and suggests that, beyond monogenic defects, aggregated rare-variant burden may also contribute to male infertility. These findings refine the genetic basis of asthenoteratozoospermia, supporting precise molecular diagnosis, individualized prognostic counseling, and informed use of assisted reproduction (e.g. ICSI) in affected couples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>This work was supported by Sidra Medicine grant SDR400185 (to M.A.A.), the FERTILITY-IQ Study and Qatar National Research Fund (QNRF) grant NPRP12S-0318-190394 (to M.A.A. and K.F.), the Qatar Research, Development and Innovation (QRDI) grant GSRA12-I-0311-250014 (to M.A.Abd.), the Quaid-i-Azam University Research Project (URF-QAU) 2020-21 (to I.U.), Japan Society for the Promotion of Science KAKENHI grants JP24K12461 (to H.K.), JP23K18328 (to H.M.), and JP21H05033 and JP23K20043 (to M.I.), Japan Agency for Medical Research and Development (AMED) grants JP23jf0126001 and JP26gn0110011 (to M.I.), and JSRM Ferting Grant 2025 (to H.K.). Open access funding was provided by the Qatar National Library.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCLOSURES<\/jats:title>\n                    <jats:p>The authors declare no competing interests.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deag154","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:53:08Z","timestamp":1792626788000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss-of-function variants in\n                    <i>CFAP57<\/i>\n                    ,\n                    <i>SEPTIN4<\/i>\n                    ,\n                    <i>SPEM2<\/i>\n                    , and\n                    <i>CFAP46<\/i>\n                    cause asthenoteratozoospermia"],"prefix":"10.1093","author":[{"given":"Shoaib","family":"Nawaz","sequence":"first","affiliation":[{"name":"Laboratory of Reproductive Biology, Translational Medicine, Sidra Medicine , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Kitakaze","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, The University of Osaka, Suita Department of Experimental Genome Research, , Osaka,","place":["Japan"]},{"name":"Department of Urology, Graduate School of Medicine, The University of Osaka , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha A","family":"Abdulla","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive Biology, Translational Medicine, Sidra Medicine , Doha, Qatar"},{"name":"Faculty of Life Sciences and Medicine, King\u2019s College London , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nida","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Hayatabad Medical Complex , Peshawar,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-5803","authenticated-orcid":false,"given":"Haruhiko","family":"Miyata","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, The University of Osaka, Suita Department of Experimental Genome Research, , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Nadhir","family":"Djekidel","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive Biology, Translational Medicine, Sidra Medicine , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar","family":"Ata","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive Biology, Translational Medicine, Sidra Medicine , Doha, Qatar"},{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kaneda","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, The University of Osaka, Suita Department of Experimental Genome Research, , Osaka,","place":["Japan"]},{"name":"Graduate School of Pharmaceutical Sciences, The University of Osaka, Suita , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hammal","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University , Islamabad,","place":["Pakistan"]},{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University , Islamabad,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University , Islamabad,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Esteves","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive Biology, Translational Medicine, Sidra Medicine , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geethanjali","family":"Devadoss Gandhi","sequence":"additional","affiliation":[{"name":"Laboratory of Genomic Medicine, Translational Medicine, Sidra Medicine , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Choucair","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Unit, Sidra Medicine , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabir","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University , Islamabad,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elbay","family":"Aliyev","sequence":"additional","affiliation":[{"name":"Laboratory of Genomic Medicine, Translational Medicine, Sidra Medicine , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Hatanaka","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, The University of Osaka, Suita Department of Experimental Genome Research, , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuma","family":"Kujime","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medicine, The University of Osaka , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go","family":"Tsujimura","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medicine, The University of Osaka , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Imanaka","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medicine, The University of Osaka , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0564-6404","authenticated-orcid":false,"given":"Sohei","family":"Kuribayashi","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medicine, The University of Osaka , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norichika","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medicine, The University of Osaka , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed M","family":"Arafa","sequence":"additional","affiliation":[{"name":"Department of Urology, Hamad Medical Corporation , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitham T","family":"Elbardisi","sequence":"additional","affiliation":[{"name":"Department of Urology, Hamad Medical Corporation , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Takezawa","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medicine, The University of Osaka , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1336-4316","authenticated-orcid":false,"given":"Shinichiro","family":"Fukuhara","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medicine, The University of Osaka , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Nonomura","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medicine, The University of Osaka , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbirami","family":"Sathappan","sequence":"additional","affiliation":[{"name":"Deep Phenotyping Core, Advanced Imaging Lab, Translational Medicine, Sidra Medicine , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Rahman","family":"Salhab","sequence":"additional","affiliation":[{"name":"Genomic Data Science Core, Sidra Medicine , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9543-042X","authenticated-orcid":false,"given":"Johnny","family":"Awwad","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Unit, Sidra Medicine , Doha, Qatar"},{"name":"Department of Genetic Medicine, Weill Cornell Medicine , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University , Islamabad,","place":["Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Fakhro","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University , Doha, Qatar"},{"name":"Laboratory of Genomic Medicine, Translational Medicine, Sidra Medicine , Doha, Qatar"},{"name":"Department of Genetic Medicine, Weill Cornell Medicine , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9859-6217","authenticated-orcid":false,"given":"Masahito","family":"Ikawa","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases, The University of Osaka, Suita Department of Experimental Genome Research, , Osaka,","place":["Japan"]},{"name":"Graduate School of Pharmaceutical Sciences, The University of Osaka, Suita , Osaka,","place":["Japan"]},{"name":"The Institute of Medical Science, The University of Tokyo, Minato-ku Laboratory of Reproductive Systems Biology, , Tokyo,","place":["Japan"]},{"name":"Center for Infectious Disease Education and Research, The University of Osaka, Suita , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0104-3304","authenticated-orcid":false,"given":"Matteo A","family":"Avella","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive Biology, Translational Medicine, Sidra Medicine , Doha, Qatar"},{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University , Doha, Qatar"},{"name":"Department of Biomedical Sciences, Qatar University , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"2026102121420785000_deag154-B1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male infertility","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet"},{"key":"2026102121420785000_deag154-B2","first-page":"100528","article-title":"Arab founder variants: contributions to clinical genomics and precision medicine","volume":"6","author":"AlAbdi","year":"2025","journal-title":"Med N Y N"},{"key":"2026102121420785000_deag154-B3","first-page":"3904","article-title":"A FAP46 mutant provides new insights into the function and assembly of the C1d complex of the ciliary central apparatus","volume":"125","author":"Brown","year":"2012","journal-title":"J Cell Sci"},{"key":"2026102121420785000_deag154-B4","doi-asserted-by":"crossref","first-page":"jcs264168","DOI":"10.1242\/jcs.264168","article-title":"Molecular models of the sperm head-tail coupling apparatus","volume":"138","author":"Buglak","year":"2025","journal-title":"J Cell Sci"},{"key":"2026102121420785000_deag154-B5","doi-asserted-by":"crossref","first-page":"e1008691","DOI":"10.1371\/journal.pgen.1008691","article-title":"Mutation of CFAP57, a protein required for the asymmetric targeting of a subset of inner dynein arms in Chlamydomonas, causes primary ciliary dyskinesia","volume":"16","author":"Bustamante-Marin","year":"2020","journal-title":"PLoS Genet"},{"key":"2026102121420785000_deag154-B6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"key":"2026102121420785000_deag154-B7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00018-025-05583-2","article-title":"CFAP65 is essential for C2a projection integrity in axonemes: implications for organ-specific ciliary dysfunction and infertility","volume":"82","author":"Chen","year":"2025","journal-title":"Cell Mol Life Sci"},{"key":"2026102121420785000_deag154-B8","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1186\/s12967-024-05162-2","article-title":"Conserved genes regulating human sex differentiation, gametogenesis and fertilization","volume":"22","author":"Fakhro","year":"2024","journal-title":"J Transl Med"},{"key":"2026102121420785000_deag154-B9","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/gim.2018.10","article-title":"Point-of-care whole-exome sequencing of idiopathic male infertility","volume":"20","author":"Fakhro","year":"2018","journal-title":"Genet Med"},{"key":"2026102121420785000_deag154-B10","doi-asserted-by":"crossref","first-page":"13298","DOI":"10.1038\/ncomms13298","article-title":"C14ORF39\/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility","volume":"7","author":"G\u00f3mez-H","year":"2016","journal-title":"Nat Commun"},{"key":"2026102121420785000_deag154-B11","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1093\/humrep\/deaa347","article-title":"Deleterious variants in genes regulating mammalian reproduction in Neanderthals, Denisovans and extant humans","volume":"36","author":"Greer","year":"2021","journal-title":"Hum Reprod"},{"key":"2026102121420785000_deag154-B12","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.cub.2012.01.031","article-title":"Proteomic analysis of mammalian primary cilia","volume":"22","author":"Ishikawa","year":"2012","journal-title":"Curr Biol"},{"key":"2026102121420785000_deag154-B13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mrd.10179","article-title":"Intramanchette transport (IMT): managing the making of the spermatid head, centrosome, and tail","volume":"63","author":"Kierszenbaum","year":"2002","journal-title":"Mol Reprod Dev"},{"key":"2026102121420785000_deag154-B14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1530\/REP-17-0184","article-title":"Spermatogonial deubiquitinase USP9X is essential for proper spermatogenesis in mice","volume":"154","author":"Kishi","year":"2017","journal-title":"Reproduction"},{"key":"2026102121420785000_deag154-B15","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.devcel.2005.01.021","article-title":"The Sept4 septin locus is required for sperm terminal differentiation in mice","volume":"8","author":"Kissel","year":"2005","journal-title":"Dev Cell"},{"key":"2026102121420785000_deag154-B16","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1128\/MCB.00354-07","article-title":"Primary ciliary dyskinesia in mice lacking the novel ciliary protein Pcdp1","volume":"28","author":"Lee","year":"2008","journal-title":"Mol Cell Biol"},{"key":"2026102121420785000_deag154-B17","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s00018-024-05147-w","article-title":"Spem2, a novel testis-enriched gene, is required for spermiogenesis and fertilization in mice","volume":"81","author":"Li","year":"2024","journal-title":"Cell Mol Life Sci"},{"key":"2026102121420785000_deag154-B18","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.ajhg.2011.07.015","article-title":"A general framework for detecting disease associations with rare variants in sequencing studies","volume":"89","author":"Lin","year":"2011","journal-title":"Am J Hum Genet"},{"key":"2026102121420785000_deag154-B19","doi-asserted-by":"crossref","first-page":"e166869","DOI":"10.1172\/jci.insight.166869","article-title":"Loss-of-function mutations in CFAP57 cause multiple morphological abnormalities of the flagella in humans and mice","volume":"8","author":"Ma","year":"2023","journal-title":"JCI Insight"},{"key":"2026102121420785000_deag154-B20","doi-asserted-by":"crossref","first-page":"e75373","DOI":"10.7554\/eLife.75373","article-title":"Oligogenic heterozygous inheritance of sperm abnormalities in mouse","volume":"11","author":"Martinez","year":"2022","journal-title":"eLife"},{"key":"2026102121420785000_deag154-B21","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1091\/mbc.e15-02-0121","article-title":"CFAP54 is required for proper ciliary motility and assembly of the central pair apparatus in mice","volume":"26","author":"McKenzie","year":"2015","journal-title":"Mol Biol Cell"},{"key":"2026102121420785000_deag154-B22","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.fertnstert.2011.11.003","article-title":"Normal live birth after testicular sperm extraction and intracytoplasmic sperm injection in variant primary ciliary dyskinesia with completely immotile sperm and structurally abnormal sperm tails","volume":"97","author":"McLachlan","year":"2012","journal-title":"Fertil Steril"},{"key":"2026102121420785000_deag154-B23","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1093\/humrep\/del130","article-title":"Outcome of ICSI with ejaculated spermatozoa in a series of men with distinct ultrastructural flagellar abnormalities","volume":"21","author":"Mitchell","year":"2006","journal-title":"Hum Reprod"},{"key":"2026102121420785000_deag154-B24","doi-asserted-by":"crossref","first-page":"dev202838","DOI":"10.1242\/dev.202838","article-title":"Development of functional spermatozoa in mammalian spermiogenesis","volume":"151","author":"Miyata","year":"2024","journal-title":"Development"},{"key":"2026102121420785000_deag154-B25","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1530\/REP-11-0245","article-title":"Postnatal testicular development in mouse species with different levels of sperm competition","volume":"143","author":"Montoto","year":"2012","journal-title":"Reproduction"},{"key":"2026102121420785000_deag154-B26","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1093\/humrep\/12.7.1497","article-title":"Successful intracytoplasmic sperm injection with spermatozoa from a patient with dysplasia of the fibrous sheath and chronic respiratory disease","volume":"12","author":"Olmedo","year":"1997","journal-title":"Hum Reprod"},{"key":"2026102121420785000_deag154-B27","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.ajhg.2010.04.005","article-title":"Pooled association tests for rare variants in exon-resequencing studies","volume":"86","author":"Price","year":"2010","journal-title":"Am J Hum Genet"},{"key":"2026102121420785000_deag154-B28","doi-asserted-by":"crossref","first-page":"6298","DOI":"10.1128\/MCB.22.17.6298-6305.2002","article-title":"Male infertility, impaired sperm motility, and hydrocephalus in mice deficient in sperm-associated antigen 6","volume":"22","author":"Sapiro","year":"2002","journal-title":"Mol Cell Biol"},{"key":"2026102121420785000_deag154-B29","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1242\/jcs.059949","article-title":"Functional transformation of the chromatoid body in mouse spermatids requires testis-specific serine\/threonine kinases","volume":"123","author":"Shang","year":"2010","journal-title":"J Cell Sci"},{"key":"2026102121420785000_deag154-B30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00439-020-02113-x","article-title":"The genetic architecture of morphological abnormalities of the sperm tail","volume":"140","author":"Tour\u00e9","year":"2021","journal-title":"Hum Genet"},{"key":"2026102121420785000_deag154-B31","doi-asserted-by":"crossref","first-page":"14222","DOI":"10.1073\/pnas.0405535101","article-title":"Comparative PRKAR1A genotype-phenotype analyses in humans with Carney complex and prkar1a haploinsufficient mice","volume":"101","author":"Veugelers","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026102121420785000_deag154-B32","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1002\/humu.24475","article-title":"Biallelic loss-of-function mutations in SEPTIN4 (C17ORF47), encoding a conserved annulus protein, cause thin midpiece spermatozoa and male infertility in humans","volume":"43","author":"Wang","year":"2022","journal-title":"Hum Mutat"},{"key":"2026102121420785000_deag154-B33","doi-asserted-by":"crossref","first-page":"jcs261962","DOI":"10.1242\/jcs.261962","article-title":"MYCBPAP is a central apparatus protein required for centrosome-nuclear envelope docking and sperm tail biogenesis in mice","volume":"137","author":"Wang","year":"2024","journal-title":"J Cell Sci"},{"key":"2026102121420785000_deag154-B34","doi-asserted-by":"crossref","first-page":"8238","DOI":"10.1038\/s41467-025-63705-7","article-title":"Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility","volume":"16","author":"Wang","year":"2025","journal-title":"Nat Commun"},{"key":"2026102121420785000_deag154-B35","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4103\/aja.aja_53_19","article-title":"Insight on multiple morphological abnormalities of sperm flagella in male infertility: what is new?","volume":"22","author":"Wang","year":"2020","journal-title":"Asian J Androl"},{"key":"2026102121420785000_deag154-B36","doi-asserted-by":"crossref","first-page":"2400790","DOI":"10.1183\/13993003.00790-2024","article-title":"Pathogenic variants in CFAP46, CFAP54, CFAP74 and CFAP221 cause primary ciliary dyskinesia with a defective C1d projection of the central apparatus","volume":"64","author":"Wohlgemuth","year":"2024","journal-title":"Eur Respir J"},{"key":"2026102121420785000_deag154-B37","volume-title":"WHO Laboratory Manual for the Examination and Processing of Human Semen","author":"World Health Organization","year":"2021","edition":"6th edn"},{"key":"2026102121420785000_deag154-B38","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\u2013tail conjunction","volume":"112","author":"Yuan","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026102121420785000_deag154-B39","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1093\/bioinformatics\/btw079","article-title":"RVTESTS: an efficient and comprehensive tool for rare variant association analysis using sequence data","volume":"32","author":"Zhan","year":"2016","journal-title":"Bioinformatics"},{"key":"2026102121420785000_deag154-B40","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1016\/j.cell.2023.05.009","article-title":"Structures of sperm flagellar doublet microtubules expand the genetic spectrum of male infertility","volume":"186","author":"Zhou","year":"2023","journal-title":"Cell"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/advance-article-pdf\/doi\/10.1093\/humrep\/deag154\/72259729\/deag154.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/advance-article-pdf\/doi\/10.1093\/humrep\/deag154\/72259729\/deag154.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:42:17Z","timestamp":1792633337000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/advance-article\/doi\/10.1093\/humrep\/deag154\/8965474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,21]]},"references-count":40,"URL":"https:\/\/doi.org\/10.1093\/humrep\/deag154","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,21]]},"article-number":"deag154"}}