{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:32:56Z","timestamp":1787841176852,"version":"build-2784847793"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"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                    Infertility is a global concern, and oligoasthenoteratozoospermia (OAT) is the most severe form of male infertility, characterized by reduced sperm count, decreased motility, and increased abnormal morphology. Multiple morphological abnormalities of the sperm flagella (MMAF) characterize the most severe type of OAT and are usually caused by loss-of-function mutations in the genes essential for vital aspects of sperm biology, including concentration, motility, and morphology. The fibrous sheath interacting protein 2 (FSIP2) plays an essential role in sperm flagellar structure and function by regulating such processes as intraflagellar transport and acrosome formation. The present study, employing whole-exome sequencing (WES), identified two\n                    <jats:italic toggle=\"yes\">FSIP2<\/jats:italic>\n                    mutations in one patient (patient 1), a homozygous missense (c.262C&gt;A, p.P88T) and a homozygous frameshift mutation (c.10948_10951del, p.N3653Nfs*22), as well as a homozygous\n                    <jats:italic toggle=\"yes\">FSIP2<\/jats:italic>\n                    frameshift mutation (c.15982_15982del, p.I5328Lfs*33) in another patient (patient 2). The results of bioinformatics analysis indicate that the identified missense mutation (c.262C&gt;A) is rare and predicted to have a deleterious effect on FSIP2. Transmission electron microscopy analysis of sperm revealed several abnormalities, including a disorganized mitochondrial sheath, absence of the central pair and some doublets of microtubules, and significant dysplasia of the fibrous sheath. Reverse transcription-polymerase chain reaction (RT-PCR) indicated significantly reduced\n                    <jats:italic toggle=\"yes\">FSIP2<\/jats:italic>\n                    messenger RNA (mRNA) levels in sperm lysate of the affected individuals. Immunofluorescence staining revealed a complete absence of FSIP2, A-kinase anchor protein 4 (AKAP4), sperm-associated antigen 6 (SPAG6), intraflagellar transport 20 (IFT20) and actin-like 7A (ACTL7A) proteins in the spermatozoa of patients. Thus, the novel\n                    <jats:italic toggle=\"yes\">FSIP2<\/jats:italic>\n                    variants identified in patient 1 and patient 2 are recognized as pathogenic mutations responsible for MMAF, providing valuable insights for genetic counseling and reproductive decision-making in affected males.\n                  <\/jats:p>","DOI":"10.4103\/aja202542","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T08:00:08Z","timestamp":1758268808000},"page":"205-212","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Novel mutations in FSIP2 cause male infertility through multiple morphological abnormalities of the sperm flagella"],"prefix":"10.4103","volume":"28","author":[{"given":"Mujahid","family":"Hussain","sequence":"first","affiliation":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, 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":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, 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":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, 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":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghulam","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, 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":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umair","family":"Shafiq","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, 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":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazal","family":"Rahim","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisar","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurang","family":"Zeb","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, 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":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasim","family":"Shah","sequence":"additional","affiliation":[{"name":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, 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":"Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"R1-20260309","doi-asserted-by":"crossref","first-page":"e12888","DOI":"10.1111\/and.12888","article-title":"Association between obesity and sperm quality","volume":"50","author":"Ramaraju","year":"2018","journal-title":"Andrologia"},{"key":"R2-20260309","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4103\/aja.aja_17_21","article-title":"Random 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