{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:46:57Z","timestamp":1784634417087,"version":"3.55.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PRG1021"],"award-info":[{"award-number":["PRG1021"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Male factor infertility concerns 7\u201310% of men and among these 40\u201360% remain unexplained.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Sources of data<\/jats:title>\n                  <jats:p>This review is based on recent published literature regarding the genetic causes of male infertility.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Areas of agreement<\/jats:title>\n                  <jats:p>Screening for karyotype abnormalities, biallelic pathogenic variants in the CFTR gene and Y-chromosomal microdeletions have been routine in andrology practice for &amp;gt;20\u00a0years, explaining ~10% of infertility cases. Rare specific conditions, such as congenital hypogonadotropic hypogonadism, disorders of sex development and defects of sperm morphology and motility, are caused by pathogenic variants in recurrently affected genes, which facilitate high diagnostic yield (40\u201360%) of targeted gene panel-based testing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Areas of controversy<\/jats:title>\n                  <jats:p>Progress in mapping monogenic causes of quantitative spermatogenic failure, the major form of male infertility, has been slower. No \u2018recurrently\u2019 mutated key gene has been identified and worldwide, a few hundred patients in total have been assigned a possible monogenic cause.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Growing points<\/jats:title>\n                  <jats:p>Given the high genetic heterogeneity, an optimal approach to screen for heterogenous genetic causes of spermatogenic failure is sequencing exomes or in perspective, genomes. Clinical guidelines developed by multidisciplinary experts are needed for smooth integration of expanded molecular diagnostics in the routine management of infertile men.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Areas timely for developing research<\/jats:title>\n                  <jats:p>Di\u2212\/oligogenic causes, structural and common variants implicated in multifactorial inheritance may explain the \u2018hidden\u2019 genetic factors. It is also critical to understand how the recently identified diverse genetic factors of infertility link to general male health concerns across lifespan and how the clinical assessment could benefit from this knowledge.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bmb\/ldab025","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T12:34:21Z","timestamp":1632400461000},"page":"5-22","source":"Crossref","is-referenced-by-count":28,"title":["Translational aspects of novel findings in genetics of male infertility\u2014status quo 2021"],"prefix":"10.1093","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8519-243X","authenticated-orcid":false,"given":"Maris","family":"Laan","sequence":"first","affiliation":[{"name":"Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, 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