{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:47:11Z","timestamp":1792176431631,"version":"4.4.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>\n                    Male infertility is often linked to genetic mutations that impair sperm motility and morphology. Multiple morphological abnormalities of the sperm flagella (MMAF) are recognized as a significant cause of male infertility and are characterized by a spectrum of structural defects. However, the underlying etiology of MMAF remains largely unknown. In this study, we recruited a consanguineous family with a history of primary male infertility affecting two brothers diagnosed with MMAF, without obvious signs of primary ciliary dyskinesia. Whole-exome sequencing and Sanger sequencing were used to identify potentially pathogenic variants, and the effects of the identified mutation were evaluated\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    . Papanicolaou staining, scanning electron microscopy, and transmission electron microscopy were performed to analyze sperm morphology. The localization and expression of outer dense fiber 2 (ODF2) in spermatozoa were examined by immunofluorescence and Western blot. We identified a novel homozygous missense mutation, c.539G&gt;A (p.R180K), in\n                    <jats:italic toggle=\"yes\">ODF2<\/jats:italic>\n                    in the two infertile brothers. Sanger sequencing confirmed autosomal recessive inheritance. The patients exhibited asthenoteratozoospermia, with abnormal flagellar morphology and reduced motility. Further ultrastructural analysis revealed axonemal disorganization consistent with MMAF. Although the identified\n                    <jats:italic toggle=\"yes\">ODF2<\/jats:italic>\n                    mutation did not affect the overall protein expression, the mutant ODF2 protein was absent from the sperm flagella. Cell transfection experiments demonstrated the aberrant localization of the mutated protein, and bioinformatics analyses predicted the disruption of a conserved residue within a coiled-coil domain of ODF2. This study underscores the pivotal role of ODF2 in sperm flagellar development and broadens the mutational spectrum associated with human MMAF.\n                  <\/jats:p>","DOI":"10.4103\/aja202627","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:00:06Z","timestamp":1792173606000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["A novel homozygous missense ODF2 variant in infertile siblings with multiple morphological abnormalities of the sperm flagella"],"prefix":"10.4103","author":[{"given":"Ghulam","family":"Mustafa","sequence":"first","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Lateef","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanveer","family":"Abbas","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musavir","family":"Abbas","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mujahid","family":"Hussain","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Shoaib","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abu","family":"Mansoor","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meftah","family":"Uddin","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousuf","family":"Raza","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansar","family":"Hussain","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sui-Xing","family":"Fan","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Hua","family":"Shi","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, 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