{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:22:35Z","timestamp":1790965355683,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1003900 2019YFA0802600 2018YFC1004700"],"award-info":[{"award-number":["2018YFC1003900 2019YFA0802600 2018YFC1004700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31630050 31890780 32061143006 82071709 31871514"],"award-info":[{"award-number":["31630050 31890780 32061143006 82071709 31871514"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["YD2070002006"],"award-info":[{"award-number":["YD2070002006"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Multiple morphological abnormalities of the flagella (MMAF) can lead to male infertility due to impaired sperm motility and morphology. Calmodulin- and spoke-associated complex (CSC) are known for their roles in radial spoke (RS) assembly and ciliary motility in Chlamydomonas, while the role of cilia- and flagella-associated protein 61 (CFAP61), a mammalian ortholog of the CSC subunits, in humans is yet unknown. Here, we recruited three unrelated Pakistani families comprising of 11 infertile male patients diagnosed with MMAF. <jats:italic>CFAP61<\/jats:italic> variants, c.451_452del (p.I151Nfs*4) in family 1 and c.847C &amp;gt; T (p.R283*) in family 2 and 3, were identified recessively co-segregating with the MMAF phenotype. Transmission electron microscopy analyses revealed severe disorganized axonemal ultrastructures, and missings of central pair, RSs, and inner dynein arms were also observed and confirmed by immunofluorescence staining in spermatozoa from patients. CFAP61 and CFAP251 signals were absent from sperm tails of the patients, which suggested the loss of functional CSC in sperm flagella. Altogether, our findings report that homozygous variants in <jats:italic>CFAP61<\/jats:italic> are associated with MMAF and male infertility, demonstrating the essential role of this gene in normal sperm flagellum structure in humans.<\/jats:p>","DOI":"10.3389\/fcell.2021.803818","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T04:50:40Z","timestamp":1643604640000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["Biallelic Variants in CFAP61 Cause Multiple Morphological Abnormalities of the Flagella and Male Infertility"],"prefix":"10.3389","volume":"9","author":[{"given":"Ao","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurang","family":"Zeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imtiaz","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daren","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asad","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianteng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjha","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasim","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haider","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Rafay","family":"Javed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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. 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