{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:32:57Z","timestamp":1791955977866,"version":"4.3.4"},"reference-count":12,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFA0802600"],"award-info":[{"award-number":["2019YFA0802600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2702601"],"award-info":[{"award-number":["2022YFC2702601"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA0806303"],"award-info":[{"award-number":["2022YFA0806303"]}],"id":[{"id":"10.13039\/501100012166","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\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32061143006"],"award-info":[{"award-number":["32061143006"]}],"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":["82171599"],"award-info":[{"award-number":["82171599"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Male infertility affects more than 20\u2009million men worldwide and is a major public health concern. Male infertility has a strong genetic basis, particularly for those unexplained cases. Here, through genetic analysis of three Pakistani families having eight infertile men with normal parameters in routine semen analysis, we identified a novel\n                    <jats:italic>ACTL7A<\/jats:italic>\n                    variant (c.149_150del, p.E50Afs*6), recessively co\u2010segregating with infertility in these three families. This variant leads to the loss of ACTL7A proteins in spermatozoa from patients. Transmission EM analyses revealed acrosome detachment from nuclei in 98.9% spermatozoa of patients. Interestingly, this\n                    <jats:italic>ACTL7A<\/jats:italic>\n                    variant was frequently detected in our sequenced Pakistani Pashtuns with a minor allele frequency of ~0.021 and all the carriers shared a common haplotype of about 240\u2009kb flanking\n                    <jats:italic>ACTL7A<\/jats:italic>\n                    , indicating that it is likely originated from a single founder. Our findings reveal that a founder\n                    <jats:italic>ACTL7A<\/jats:italic>\n                    pathogenic variant confers a high genetic susceptibility for male infertility with normal routine semen parameters but acrosomal ultrastructural defects in Pakistani Pashtun descendants, and highlight that variants not rare should also be considered when trying to identify disease\u2010causing variants in ethnic groups with the tradition of intra\u2010ethnic marriages.\n                  <\/jats:p>","DOI":"10.1111\/cge.14383","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:37:01Z","timestamp":1686184621000},"page":"564-570","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A recessive\n                    <scp>\n                      <i>ACTL7A<\/i>\n                    <\/scp>\n                    founder variant leads to male infertility due to acrosome detachment in\n                    <scp>Pakistani Pashtuns<\/scp>"],"prefix":"10.1111","volume":"104","author":[{"given":"Jianteng","family":"Zhou","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurang","family":"Zeb","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Ma","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daren","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5552-6443","authenticated-orcid":false,"given":"Fazal","family":"Rahim","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjha","family":"Khan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan","family":"Khan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mian Basit Shah","family":"Kakakhel","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asad","family":"Khan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei 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of Science and Technology of China  Hefei 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 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Yang","sequence":"additional","affiliation":[{"name":"The Center for Clinical Reproductive Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei 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, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Shi","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Hefei National Research Center for Physical Sciences at the Microscale, Institute of Health and Medicine, Hefei Comprehensive National Science Center University of Science and Technology of China  Hefei 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