{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:27:46Z","timestamp":1790616466087,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acephalic spermatozoa syndrome (ASS) is a rare but extremely severe type of teratozoospermia, defined by the presence of a majority of headless flagella and a minority of tail-less sperm heads in the ejaculate. Like the other severe monomorphic teratozoospermias, ASS has a strong genetic basis and is most often caused by bi-allelic variants in SUN5 (Sad1 and UNC84 domain-containing 5). Using whole exome sequencing (WES), we investigated a cohort of nine infertile subjects displaying ASS. These subjects were recruited in three centers located in France and Tunisia, but all originated from North Africa. Sperm from subjects carrying candidate genetic variants were subjected to immunofluorescence analysis and transmission electron microscopy. Moreover, fluorescent in situ hybridization (FISH) was performed on sperm nuclei to assess their chromosomal content. Variant filtering permitted us to identify the same SUN5 homozygous frameshift variant (c.211+1_211+2dup) in 7\/9 individuals (78%). SUN5 encodes a protein localized on the posterior part of the nuclear envelope that is necessary for the attachment of the tail to the sperm head. Immunofluorescence assays performed on sperm cells from three mutated subjects revealed a total absence of SUN5, thus demonstrating the deleterious impact of the identified variant on protein expression. Transmission electron microscopy showed a conserved flagellar structure and a slightly decondensed chromatin. FISH did not highlight a higher rate of chromosome aneuploidy in spermatozoa from SUN5 patients compared to controls, indicating that intra-cytoplasmic sperm injection (ICSI) can be proposed for patients carrying the c.211+1_211+2dup variant. These results suggest that the identified SUN5 variant is the main cause of ASS in the North African population. Consequently, a simple and inexpensive genotyping of the 211+1_211+2dup variant could be beneficial for affected men of North African origin before resorting to more exhaustive genetic analyses.<\/jats:p>","DOI":"10.3390\/ijms22042187","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T14:23:27Z","timestamp":1614003807000},"page":"2187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8962-3447","authenticated-orcid":false,"given":"Caroline","family":"Cazin","sequence":"first","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM, CNRS, Universit\u00e9 Grenoble Alpes, F-38000 Grenoble, France"},{"name":"UM GI-DPI, CHU Grenoble Alpes, F-38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2381-443X","authenticated-orcid":false,"given":"Yasmine","family":"Boumerdassi","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology, H\u00f4pital Jean Verdier, Assistance Publique, H\u00f4pitaux de Paris, F-75004 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Martinez","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM, CNRS, Universit\u00e9 Grenoble Alpes, F-38000 Grenoble, France"},{"name":"UM de G\u00e9n\u00e9tique Chromosomique, CHU Grenoble Alpes, F-38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selima","family":"Fourati Ben Mustapha","sequence":"additional","affiliation":[{"name":"Centre d\u2019Aide M\u00e9dicale \u00e0 la Procr\u00e9ation, Polyclinique les Jasmin, Centre Urbain Nord, Tunis 1003, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Whitfield","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM, CNRS, Universit\u00e9 Grenoble Alpes, F-38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Coutton","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM, CNRS, Universit\u00e9 Grenoble Alpes, F-38000 Grenoble, France"},{"name":"Department of Reproductive Biology, H\u00f4pital Jean Verdier, Assistance Publique, H\u00f4pitaux de Paris, F-75004 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Thierry-Mieg","sequence":"additional","affiliation":[{"name":"TIMC-IMAG, CNRS, Universit\u00e9 Grenoble Alpes, F-38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Di Pizio","sequence":"additional","affiliation":[{"name":"EA 4308 \u2018Gametogenesis and Gamete Quality, Normandie University, UNIROUEN, F-76000 Rouen, France"},{"name":"Reproductive Biology Laboratory-CECOS, Assisted Reproductive Center, Rouen Normandy University Hospital, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Rives","sequence":"additional","affiliation":[{"name":"EA 4308 \u2018Gametogenesis and Gamete Quality, Normandie University, UNIROUEN, F-76000 Rouen, France"},{"name":"Reproductive Biology Laboratory-CECOS, Assisted Reproductive Center, Rouen Normandy University Hospital, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Arnoult","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM, CNRS, Universit\u00e9 Grenoble Alpes, F-38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5629-849X","authenticated-orcid":false,"given":"Aminata","family":"Tour\u00e9","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM, CNRS, Universit\u00e9 Grenoble Alpes, F-38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1544-7449","authenticated-orcid":false,"given":"Pierre F.","family":"Ray","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM, CNRS, Universit\u00e9 Grenoble Alpes, F-38000 Grenoble, France"},{"name":"UM GI-DPI, CHU Grenoble Alpes, F-38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoudha","family":"Zouari","sequence":"additional","affiliation":[{"name":"Centre d\u2019Aide M\u00e9dicale \u00e0 la Procr\u00e9ation, Polyclinique les Jasmin, Centre Urbain Nord, Tunis 1003, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Sifer","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology, H\u00f4pital Jean Verdier, Assistance Publique, H\u00f4pitaux de Paris, F-75004 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zine-Eddine","family":"Kherraf","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, INSERM, CNRS, Universit\u00e9 Grenoble Alpes, F-38000 Grenoble, France"},{"name":"UM GI-DPI, CHU Grenoble Alpes, F-38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mascarenhas, M.N., Flaxman, S.R., Boerma, T., Vanderpoel, S., and Stevens, G.A. 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