{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:39:38Z","timestamp":1790635178857,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201019\u2010CE17\u20100014"],"award-info":[{"award-number":["ANR\u201019\u2010CE17\u20100014"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Non\u2010obstructive azoospermia (NOA) resulting from primary spermatogenic failure represents one of the most severe forms of male infertility, largely because therapeutic options are very limited. Beyond their diagnostic value, genetic tests for NOA also hold prognostic potential. Specifically, genetic diagnosis enables the establishment of genotype\u2010testicular phenotype correlations, which, in some cases, provide a negative predictive value for testicular sperm extraction (TESE), thereby preventing unnecessary surgical procedures. In this study, we employed whole\u2010genome sequencing (WGS) to investigate two generations of an Iranian family with NOA and identified a homozygous splicing variant in <jats:italic>TDRKH<\/jats:italic> (NM_001083965.2: c.562\u20102A&gt;T). <jats:italic>TDRKH<\/jats:italic> encodes a conserved mitochondrial membrane\u2010anchored factor essential for piRNA biogenesis in germ cells. In <jats:italic>Tdrkh<\/jats:italic> knockout mice, de\u2010repression of retrotransposons in germ cells leads to spermatogenic arrest and male infertility. Previously, our team reported <jats:italic>TDRKH<\/jats:italic> involvement in human NOA cases through the investigation of a North African cohort. This current study marks the second report of <jats:italic>TDRKH<\/jats:italic>'s role in NOA and human male infertility, underscoring the significance of the piRNA pathway in spermatogenesis. Furthermore, across both studies, we demonstrated that men carrying <jats:italic>TDRKH<\/jats:italic> variants, similar to knockout mice, exhibit complete spermatogenic arrest, correlating with failed testicular sperm retrieval.<\/jats:p>","DOI":"10.1111\/cge.14584","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T06:15:23Z","timestamp":1719987323000},"page":"625-631","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Whole genome sequencing identifies a homozygous splicing variant in <i>TDRKH<\/i> segregating with non\u2010obstructive azoospermia in an Iranian family"],"prefix":"10.1111","volume":"106","author":[{"given":"Amir","family":"Amiri\u2010Yekta","sequence":"first","affiliation":[{"name":"Department of Genetics, Reproductive Biomedicine Research Center Royan Institute for Reproductive Biomedicine, ACECR  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4980-9572","authenticated-orcid":false,"given":"Sharanya","family":"Sen","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences  Grenoble France"},{"name":"CHU Grenoble Alpes, UM GI\u2010DPI  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Hazane\u2010Puch","sequence":"additional","affiliation":[{"name":"CHU Grenoble Alpes, Medical Unit of Molecular Genetics (Hereditary Diseases and Oncology)  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9lia","family":"Tebbakh","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences  Grenoble France"},{"name":"CHU Grenoble Alpes, UM GI\u2010DPI  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Roux\u2010Buisson","sequence":"additional","affiliation":[{"name":"CHU Grenoble Alpes, Medical Unit of Molecular Genetics (Hereditary Diseases and Oncology)  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Cazin","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences  Grenoble France"},{"name":"CHU Grenoble Alpes, UM GI\u2010DPI  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Thierry\u2010Mieg","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, CNRS, UMR5525, TIMC  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Bouras","sequence":"additional","affiliation":[{"name":"Centre L\u00e9on B\u00e9rard, Laboratory of Constitutional Genetics for Frequent Cancer HCL\u2010CLB  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadighi\u2010Gilani","family":"Mohammad Ali","sequence":"additional","affiliation":[{"name":"Department of Andrology, Reproductive Biomedicine Research Center Royan Institute for Reproductive Biomedicine, ACECR  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyedeh\u2010Hanieh","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Department of Andrology, Reproductive Biomedicine Research Center Royan Institute for Reproductive Biomedicine, ACECR  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maedeh","family":"Goodarzian","sequence":"additional","affiliation":[{"name":"Department of Andrology, Reproductive Biomedicine Research Center Royan Institute for Reproductive Biomedicine, ACECR  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Gourabi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Reproductive Biomedicine Research Center Royan Institute for Reproductive Biomedicine, ACECR  Tehran Iran"}],"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":"Univ. Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences  Grenoble France"},{"name":"CHU Grenoble Alpes, UM GI\u2010DPI  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zine\u2010Eddine","family":"Kherraf","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences  Grenoble France"},{"name":"CHU Grenoble Alpes, UM GI\u2010DPI  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-018-0003-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.01.011"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2023.2171544"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaae002"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14473"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI171541"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107193"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-023-01172-y"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-022-02515-z"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2022.05.011"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35661-z"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev139"},{"key":"e_1_2_10_14_1","first-page":"1956","article-title":"Genetic dissection of spermatogenic arrest through exome analysis: clinical implications for the management of azoospermic men","volume":"22","author":"Krausz C","year":"2020","journal-title":"Genet Med off J Am Coll Med Genet"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dez042"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00528-0"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3089"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-017-7417-8_4"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.121"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1281"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14584","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T02:23:05Z","timestamp":1727835785000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,2]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/cge.14584"],"URL":"https:\/\/doi.org\/10.1111\/cge.14584","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,2]]},"assertion":[{"value":"2024-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}