{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:26:11Z","timestamp":1788542771139,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["DIVERCIL\u201017\u2010CE13\u20100023; FLAGEL\u2010OME\u201019\u2010CE17\u20100014"],"award-info":[{"award-number":["DIVERCIL\u201017\u2010CE13\u20100023; FLAGEL\u2010OME\u201019\u2010CE17\u20100014"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012952","name":"Universit\u00e9 Grenoble Alpes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012952","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Sperm flagella share an evolutionary conserved microtubule\u2010based structure with motile cilia expressed at the surface of several cell types, such as the airways epithelial cells. As a result, male infertility can be observed as an isolated condition or a syndromic trait, illustrated by Primary Cilia Dyskinesia (PCD). We report two unrelated patients showing multiple morphological abnormalities of the sperm flagella (MMAF) and carrying distinct homozygous truncating variants in the PCD\u2010associated gene\n                    <jats:italic>CCDC65<\/jats:italic>\n                    . We characterized one of the identified variants (\n                    <jats:italic>c.1208del<\/jats:italic>\n                    ; p.Asn403Ilefs*9), which induces the near absence of CCDC65 protein in patient sperm. In\n                    <jats:italic>Chlamydomonas<\/jats:italic>\n                    , CCDC65 ortholog (DRC2, FAP250) is a component of the Nexin\u2010Dynein Regulatory complex (N\u2010DRC), which interconnects microtubule doublets and coordinates dynein arms activity. In sperm cells from the patient, we also show the loss of GAS8, another component of the N\u2010DRC, supporting a structural\/functional link between the two proteins. Our work indicates that, similarly to ciliary axoneme, CCDC65 is required for sperm flagellum structure. Importantly, our work provides first evidence that mutations in the PCD\u2010associated gene\n                    <jats:italic>CCDC65<\/jats:italic>\n                    also cause asthenozoospermia.\n                  <\/jats:p>","DOI":"10.1111\/cge.14459","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T05:23:47Z","timestamp":1700198627000},"page":"317-322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["<scp>\n                      <i>CCDC65<\/i>\n                    <\/scp>\n                    , encoding a component of the axonemal\n                    <scp>Nexin\u2010Dynein<\/scp>\n                    regulatory complex, is required for sperm flagellum structure in humans"],"prefix":"10.1111","volume":"105","author":[{"given":"Fadwa","family":"Jreijiri","sequence":"first","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Universit\u00e9 Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Cavarocchi","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Universit\u00e9 Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Amiri\u2010Yekta","sequence":"additional","affiliation":[{"name":"Reproductive Biomedicine Research Center Royan Institute for Reproductive Biomedicine, ACECR  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Cazin","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Universit\u00e9 Grenoble Alpes  Grenoble France"},{"name":"CHU Grenoble Alpes, UM GI\u2010DPI, Grenoble  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyedeh\u2010Hanieh","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Reproductive Biomedicine Research Center Royan Institute for Reproductive Biomedicine, ACECR  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elma","family":"El Khouri","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM U1016, CNRS UMR8104, Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Patrat","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM U1016, CNRS UMR8104, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Biologie de la Reproduction \u2013 APHP Centre\u2010Universit\u00e9 Paris Cit\u00e9, Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Thierry\u2010Mieg","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, CNRS, UMR 5525, TIMC \/ MAGe  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1544-7449","authenticated-orcid":false,"given":"Pierre F.","family":"Ray","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Universit\u00e9 Grenoble Alpes  Grenoble France"},{"name":"CHU Grenoble Alpes, UM GI\u2010DPI, Grenoble  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Dulioust","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM U1016, CNRS UMR8104, Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Biologie de la Reproduction \u2013 APHP Centre\u2010Universit\u00e9 Paris Cit\u00e9, Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Whitfield","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Universit\u00e9 Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5629-849X","authenticated-orcid":false,"given":"Aminata","family":"Tour\u00e9","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Universit\u00e9 Grenoble Alpes  Grenoble 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