{"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":1790616466140,"version":"4.1.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Thanks to tremendous advances in sequencing technologies and in particular to whole exome sequencing (WES), many genes have now been linked to severe sperm defects. A precise genetic diagnosis is obtained for a minority of patients and only for the most severe defects like azoospermia or macrozoospermia which is very often due to defects in the aurora kinase C (\n                      <jats:italic toggle=\"yes\">AURKC<\/jats:italic>\n                      ) gene. Here, we studied a subject with a severe oligozoospermia and a phenotypic diagnosis of macrozoospermia.\n                      <jats:italic toggle=\"yes\">AURKC<\/jats:italic>\n                      analysis did not reveal any deleterious variant. WES was then initiated which permitted to identify a homozygous loss of function variant in the zinc finger MYND-type containing 15 (\n                      <jats:italic toggle=\"yes\">ZMYND15<\/jats:italic>\n                      ) gene. ZMYND15 has been described to serve as a switch for haploid gene expression, and mice devoid of ZMYND15 were shown to be sterile due to nonobstructive azoospermia (NOA). In man,\n                      <jats:italic toggle=\"yes\">ZMYND15<\/jats:italic>\n                      has been associated with NOA and severe oligozoospermia. We confirm here that the presence of a bi-allelic\n                      <jats:italic toggle=\"yes\">ZMYND15<\/jats:italic>\n                      variant induces a severe oligozoospermia. In addition, we show that severe oligozoospermia can be associated macrozoospermia, and that a phenotypic misdiagnosis is possible, potentially delaying the genetic diagnosis. In conclusion, genetic defects in\n                      <jats:italic toggle=\"yes\">ZMYND15<\/jats:italic>\n                      can induce complete NOA or severe oligozoospermia associated with a very severe teratozoospermia. In our experience, severe oligozoospermia is often associated with severe teratozoospermia and can sometimes be misinterpreted as macrozoospermia or globozoospermia. In these instances, specific\n                      <jats:italic toggle=\"yes\">AURKC<\/jats:italic>\n                      or dpy-19 like 2 (\n                      <jats:italic toggle=\"yes\">DPY19L2<\/jats:italic>\n                      ) diagnosis is usually negative and we recommend the direct use of a pan-genomic techniques such as WES.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/aja202194","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T10:42:57Z","timestamp":1641897777000},"page":"243-247","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":19,"title":["From azoospermia to macrozoospermia, a phenotypic continuum due to mutations in the ZMYND15 gene"],"prefix":"10.4103","volume":"24","author":[{"given":"Zine-Eddine","family":"Kherraf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Cazin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lestrade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Muronova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Coutton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Arnoult","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Thierry-Mieg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre F","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-4-20240829","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF02889540","article-title":"Multi-tailed spermatozoa in a case with asthenospermia and teratospermia","volume":"26","author":"Nistal","year":"1977","journal-title":"Virchows Arch B Cell Pathol"},{"key":"R2-4-20240829","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/cge.12905","article-title":"Genetic abnormalities leading to qualitative defects of sperm morphology or function","volume":"91","author":"Ray","year":"2017","journal-title":"Clin Gene"},{"key":"R3-4-20240829","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/molehr\/2.9.665","article-title":"Rapid chromosomal analysis of germ-line cells by FISH: an investigation of an infertile male with large-headed 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