{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:32:55Z","timestamp":1791361975320,"version":"4.3.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31630050"],"award-info":[{"award-number":["31630050"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31890780"],"award-info":[{"award-number":["31890780"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31871514"],"award-info":[{"award-number":["31871514"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2017LH012"],"award-info":[{"award-number":["ZR2017LH012"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Multiple morphological abnormalities of the flagella (MMAF) is a genetically heterogeneous disorder leading to male infertility. Recent studies have revealed that\n                    <jats:italic>DNAH17<\/jats:italic>\n                    variants are associated with MMAF, yet there is no functional evidence in support of their pathnogenicity. Here, we recruited two consanguineous families of Pakistani and Chinese origins, respectively, diagnosed with MMAF. Whole\u2010exome sequencing identified novel homozygous\n                    <jats:italic>DNAH17<\/jats:italic>\n                    variants, which led to loss of DNAH17 proteins, in the patients. Transmission electron microscope analyses revealed completely disorganized axonemal structure as the predominant anomaly and increased frequencies of missings of microtubule doublet(s) 4\u20137 in sperm flagella of patients. Similar to those found in patients,\n                    <jats:italic>Dnah17<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice also displayed MMAF phenotype along with completely disorganized axonemal structures. Clusters of disorganized microtubules and outer dense fibers were observed in developing spermatids, indicating impaired sperm flagellar assembly. Besides, we also noticed many elongating spermatids with a deformed nuclear shape and abnormal step 16 spermatids that failed to spermiate, which subsequently underwent apoptosis in\n                    <jats:italic>Dnah17<\/jats:italic>\n                    \u2010null mice. These findings present direct evidence establishing that\n                    <jats:italic>DNAH17<\/jats:italic>\n                    is a MMAF\u2010related gene in humans and mice, extend the clinical interpretations of\n                    <jats:italic>DNAH17<\/jats:italic>\n                    variants, and highlight an essential and complex role of DNAH17 in spermatogenesis.\n                  <\/jats:p>","DOI":"10.1111\/cge.13866","type":"journal-article","created":{"date-parts":[[2020,10,18]],"date-time":"2020-10-18T02:30:22Z","timestamp":1602988222000},"page":"176-186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Novel loss\u2010of\u2010function variants in\n                    <scp>\n                      <i>DNAH17<\/i>\n                    <\/scp>\n                    cause multiple morphological abnormalities of the sperm flagella in humans and mice"],"prefix":"10.1111","volume":"99","author":[{"given":"Beibei","family":"Zhang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan","family":"Khan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences Fudan University  Shanghai 200011 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Ma","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asad","family":"Khan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mian Basit Shah","family":"Kakakhel","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianteng","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fudan University Pudong Medical Center, Institutes of Biomedical Sciences, The Department of Systems Biology for Medicine, School of Basic Medical Sciences Fudan University  Shanghai 200011 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim","family":"Ali","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Jiang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghulam","family":"Murtaza","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjha","family":"Khan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 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Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"The Center of Cryo\u2010Electron Microscopy (CCEM) Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences Fudan University  Shanghai 200011 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4091-5534","authenticated-orcid":false,"given":"Xiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine The Affiliated Yantai Yuhuangding Hospital of Qingdao University  Yantai 264000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0995-2345","authenticated-orcid":false,"given":"Hui","family":"Ma","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development University of Science and Technology of China  Hefei 230027 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