{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:48:58Z","timestamp":1790768938767,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T00:00:00Z","timestamp":1699660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["FLAGEL\u2010OME ANR 19\u2010CE17\u20100014"],"award-info":[{"award-number":["FLAGEL\u2010OME ANR 19\u2010CE17\u20100014"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Motile cilia and flagella are closely related organelles structured around a highly conserved axoneme whose formation and maintenance involve proteins from hundreds of genes. Defects in many of these genes have been described to induce primary ciliary dyskinesia (PCD) mainly characterized by chronic respiratory infections, situs inversus and\/or infertility. In men, cilia\/flagella\u2010related infertility is usually caused by asthenozoospermia due to multiple morphological abnormalities of the sperm flagella (MMAF). Here, we investigated a cohort of 196 infertile men displaying a typical MMAF phenotype without any other PCD symptoms. Analysis of WES data identified a single case carrying a deleterious homozygous\n                    <jats:italic>GAS8<\/jats:italic>\n                    variant altering a splice donor consensus site\n                    <jats:italic>.<\/jats:italic>\n                    This gene, also known as\n                    <jats:italic>DRC4<\/jats:italic>\n                    , encodes a subunit of the Nexin\u2010Dynein Regulatory Complex (N\u2010DRC), and has been already associated to male infertility and mild PCD. Confirming the deleterious effect of the candidate variant, GAS8 staining by immunofluorescence did not evidence any signal from the patient's spermatozoa whereas a strong signal was present along the whole flagella length in control cells. Concordant with its role in the N\u2010DRC, transmission electron microscopy evidenced peripheral microtubule doublets misalignments. We confirm here the importance of GAS8 in the N\u2010DRC and observed that its absence induces a typical MMAF phenotype not necessarily accompanied by other PCD symptoms.\n                  <\/jats:p>","DOI":"10.1111\/cge.14450","type":"journal-article","created":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T03:40:08Z","timestamp":1699674008000},"page":"220-225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A splice donor variant of\n                    <i>GAS8<\/i>\n                    induces structural disorganization of the axoneme in sperm flagella and leads to nonsyndromic male infertility"],"prefix":"10.1111","volume":"105","author":[{"given":"Zine\u2010Eddine","family":"Kherraf","sequence":"first","affiliation":[{"name":"Team Genetics Epigenetics and Therapies of Infertility (GETI) Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Univ. Grenoble Alpes  Grenoble France"},{"name":"CHU Grenoble Alpes, UM GI\u2010DPI  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Laure","family":"Barbotin","sequence":"additional","affiliation":[{"name":"CHU Lille, Institut de Biologie de la Reproduction\u2010Spermiologie\u2010CECOS  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Martinez","sequence":"additional","affiliation":[{"name":"Team Genetics Epigenetics and Therapies of Infertility (GETI) Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Univ. Grenoble Alpes  Grenoble France"},{"name":"CHU Grenoble Alpes, UM de G\u00e9n\u00e9tique Chromosomique  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Mazet","sequence":"additional","affiliation":[{"name":"Team Genetics Epigenetics and Therapies of Infertility (GETI) Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Univ. Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Cazin","sequence":"additional","affiliation":[{"name":"Team Genetics Epigenetics and Therapies of Infertility (GETI) Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Univ. Grenoble Alpes  Grenoble France"},{"name":"CHU Grenoble Alpes, UM GI\u2010DPI  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8873-8098","authenticated-orcid":false,"given":"Charles","family":"Coutton","sequence":"additional","affiliation":[{"name":"Team Genetics Epigenetics and Therapies of Infertility (GETI) Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Univ. Grenoble Alpes  Grenoble France"},{"name":"CHU Grenoble Alpes, UM de G\u00e9n\u00e9tique Chromosomique  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Arnoult","sequence":"additional","affiliation":[{"name":"Team Genetics Epigenetics and Therapies of Infertility (GETI) Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Univ. Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Thierry\u2010Mieg","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CNRS, UMR 5525, TIMC\/MAGe  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Rives","sequence":"additional","affiliation":[{"name":"Team Adrenal and Gonadal Pathophysiology Inserm, U1239 NorDIC, University Rouen Normandie  Rouen France"},{"name":"Reproductive Biology Laboratory\u2010CECOS Rouen University Hospital  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Rives\u2010Feraille","sequence":"additional","affiliation":[{"name":"Team Adrenal and Gonadal Pathophysiology Inserm, U1239 NorDIC, University Rouen Normandie  Rouen France"},{"name":"Reproductive Biology Laboratory\u2010CECOS Rouen University Hospital  Rouen 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":"Team Genetics Epigenetics and Therapies of Infertility (GETI) Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Univ. Grenoble Alpes  Grenoble France"},{"name":"CHU Grenoble Alpes, UM GI\u2010DPI  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.11.017"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1034951"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-020-02113-x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.16196"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032559"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.01.011"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.08.012"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23005"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006220"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106941200"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cm.21338"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","unstructured":"GhanaeianA MajhiS McCaffreyCL et al.Integrated modeling of the Nexin\u2010dynein regulatory complex reveals its regulatory mechanism. bioRxiv.2023.","DOI":"10.1101\/2023.05.31.543107"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e12-11-0801"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.10.044"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E17-08-0510"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab171"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072299"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-021-00985-z"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2019.04.71"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14450","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T22:04:04Z","timestamp":1705701844000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,11]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1111\/cge.14450"],"URL":"https:\/\/doi.org\/10.1111\/cge.14450","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14450\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14450\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14450\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14450\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14450\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14450\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,11]]},"assertion":[{"value":"2023-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}