{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T10:29:35Z","timestamp":1777285775930,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"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\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["FLAGELOME ANR\u201019\u2010CE17\u20100014"],"award-info":[{"award-number":["FLAGELOME ANR\u201019\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":["Andrology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Asthenozoospermia, characterized by reduced sperm motility, is a common cause of male infertility. Multiple morphological abnormalities of the sperm flagella (MMAF) represent a severe and genetically heterogeneous form of asthenozoospermia. Over 50 genes have been associated, but approximately half of MMAF cases remain unexplained. DRC1, a gene involved in the nexin\u2010dynein regulatory complex (N\u2010DRC), has been linked to MMAF and primary ciliary dyskinesia (PCD), often with significant variability in clinical presentation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      His study aimed to identify novel pathogenic\n                      <jats:italic>DRC1<\/jats:italic>\n                      variants in MMAF patients, assess their impact on sperm flagellar structure, and evaluate intracytoplasmic sperm injection (ICSI) and pregnancy outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>A cohort of 196 non\u2010syndromic MMAF patients was analyzed using whole exome sequencing (WES). Functional validation of candidate variants included immunofluorescence to assess protein expression and transmission electron microscopy (TEM) to identify ultrastructural abnormalities. Assisted reproductive therapy outcomes were also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WES identified a recurrent homozygous frameshift variant in DRC1 NM_145038.5: c.109dup; p.(Gln37ProfsTer30) in four patients (2%), all of North African origin, none of whom suffer from PCD\u2010related symptoms. The variant caused a complete absence of DRC1 protein in spermatozoa. TEM showed flagellar abnormalities, with 10% of axonemal sections revealing peripheral doublet dissociation, suggesting N\u2010DRC instability. ICSI resulted in a 68.5% fertilization rate, with three out of four couples successfully delivering healthy children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and conclusion<\/jats:title>\n                    <jats:p>The identification of a novel and recurrent pathogenic DRC1 variant broadens the mutation spectrum associated with MMAF. The absence of systemic PCD symptoms suggests that DRC1 deficiency may primarily affect spermatogenesis. Notably, the phenotypic spectrum might be influenced by the genetic background, varying across populations. Favorable ICSI outcomes, with a 68.5% fertilization rate and successful pregnancies in three out of four couples, highlight the effectiveness of assisted reproductive techniques for patients with this genetic defect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.13837","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T01:28:28Z","timestamp":1736386108000},"page":"2110-2121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A recurrent loss\u2010of\u2010function variant in\n                    <i>DRC1<\/i>\n                    causes non\u2010syndromic severe asthenozoospermia with favorable intracytoplasmic sperm injection and pregnancy outcomes"],"prefix":"10.1111","volume":"13","author":[{"given":"C\u00e9lia","family":"Tebbakh","sequence":"first","affiliation":[{"name":"Institute for Advanced Biosciences Team Genetics Epigenetics and Therapies of Infertility University of Grenoble Alpes  Grenoble France"},{"name":"CHU Grenoble Alpes UM GI\u2010DPI  Grenoble France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Laure","family":"Barbotin","sequence":"additional","affiliation":[{"name":"CHU Lille Laboratoire de Biologie de la Reproduction\u2010Spermiologie\u2010CECOS  Lille France"},{"name":"Development and Plasticity of the Neuroendocrine Brain University of Lille  Lille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7572-9096","authenticated-orcid":false,"given":"Guillaume","family":"Martinez","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences Team Genetics Epigenetics and Therapies of Infertility University of Grenoble Alpes  Grenoble France"},{"name":"CHU Grenoble Alpes UM de G\u00e9n\u00e9tique Chromosomique  Grenoble 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