{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:48:33Z","timestamp":1787071713025,"version":"build-2736575974"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>\n                    Multiple morphological abnormalities of the sperm flagella (MMAF), characterized by severe morphological sperm defects, such as absent, short, irregular caliber, and coiled flagella with extreme asthenoteratozoospermia, are the most prevalent cause of human male infertility. Previous studies have identified several genes linked to MMAF; however, the increasing incidence of infertility indicates that most affected individuals remain undiagnosed, prompting further investigation to uncover novel mutations and genes. Whole-exome sequencing (WES) was conducted on a consanguineous infertile family from Pakistan to investigate the potential monogenic inheritance pattern in individuals affected by asthenoteratozoospermia. WES identified novel homozygous variants (c.A4457G; p.K1486R, and c.C10624T; p.R3542*) in dynein heavy chain domain 1 (\n                    <jats:italic toggle=\"yes\">DNHD1<\/jats:italic>\n                    ) in the proband and his affected brother. Semen analysis revealed a low progressive motility and severe MMAF in both siblings. Hematoxylin and eosin staining, immunofluorescence, and transmission electron microscopy unveiled an abnormal axoneme structure characterized by missing central pairs, disorganized microtubule duplets, and severe mitochondrial sheath defects, which led to the low sperm progressive motility and infertility in the affected siblings. This study identified a novel biallelic nonsense variant in\n                    <jats:italic toggle=\"yes\">DNHD1<\/jats:italic>\n                    that caused MMAF in a Pakistani population, endorsing previous findings and expanding the spectrum of potential\n                    <jats:italic toggle=\"yes\">DNHD1<\/jats:italic>\n                    variants in the pathogenesis of asthenoteratozoospermia.\n                  <\/jats:p>","DOI":"10.4103\/aja202535","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T05:00:38Z","timestamp":1762837238000},"page":"179-186","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Novel biallelic DNHD1 variants associated with male infertility with severe MMAF phenotype"],"prefix":"10.4103","volume":"28","author":[{"given":"Islam","family":"Uddin","sequence":"first","affiliation":[{"name":"Center for Reproduction and Genetics, Department of 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of Anhui Province, University of Science and Technology of China (USTC), Hefei 230001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cao-Ling","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China"},{"name":"Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Laboratory for Physical Sciences at Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China (USTC), Hefei 230001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Mei","family":"Xing","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China"},{"name":"Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Laboratory for Physical Sciences at Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China (USTC), Hefei 230001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Qi","family":"Zou","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China"},{"name":"Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Laboratory for Physical Sciences at Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China (USTC), Hefei 230001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Tahmasebi","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China"},{"name":"Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Laboratory for Physical Sciences at Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China (USTC), Hefei 230001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Imran","family":"Khan","sequence":"additional","affiliation":[{"name":"Discipline of Physiology, Faculty of Animal Husbandry and Veterinary Sciences, The University of Agriculture, Peshawar 25130, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Min","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Qiang","family":"Bao","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and 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