{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:22Z","timestamp":1772160082511,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071701"],"award-info":[{"award-number":["82071701"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271639"],"award-info":[{"award-number":["82271639"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972641"],"award-info":[{"award-number":["81972641"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mediator of\n                    <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\n                    damage checkpoint 1 (MDC1)\u00a0is a protein closely associated with the repair of\n                    <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\n                    damage. Recently, we identified three novel variants (NM_014641.3:c.\n                    <jats:styled-content style=\"fixed-case\">C5977T<\/jats:styled-content>\n                    ; p.\n                    <jats:styled-content style=\"fixed-case\">R1993X<\/jats:styled-content>\n                    ) (NM_014641.3:c.\n                    <jats:styled-content style=\"fixed-case\">C5644T<\/jats:styled-content>\n                    ; p.\n                    <jats:styled-content style=\"fixed-case\">R1882X<\/jats:styled-content>\n                    ; c.\n                    <jats:styled-content style=\"fixed-case\">A1T<\/jats:styled-content>\n                    ; p.\n                    <jats:styled-content style=\"fixed-case\">M1L<\/jats:styled-content>\n                    ) in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>MDC1<\/jats:italic>\n                    <\/jats:styled-content>\n                    in two patients with severe oligoasthenoteratozoospermia (\n                    <jats:styled-content style=\"fixed-case\">OAT<\/jats:styled-content>\n                    ). In\u00a0vitro validation showed that the p.\n                    <jats:styled-content style=\"fixed-case\">R1882X<\/jats:styled-content>\n                    variant resulted in the truncation of the\n                    <jats:styled-content style=\"fixed-case\">MDC1<\/jats:styled-content>\n                    protein, and the p.\n                    <jats:styled-content style=\"fixed-case\">R1993X<\/jats:styled-content>\n                    variant resulted in the degradation of the\n                    <jats:styled-content style=\"fixed-case\">MDC1<\/jats:styled-content>\n                    protein after truncation. Immunofluorescence demonstrated that the truncated protein caused by the variants affected the colocalization relationship between\n                    <jats:styled-content style=\"fixed-case\">MDC1<\/jats:styled-content>\n                    and its interacting protein\n                    <jats:styled-content style=\"fixed-case\">\u03b3H2AX<\/jats:styled-content>\n                    . Additionally, one of the patients and his wife underwent intracytoplasmic sperm injection (\n                    <jats:styled-content style=\"fixed-case\">ICSI<\/jats:styled-content>\n                    ), but the result was unsatisfactory. We screened out the variants of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>MDC1<\/jats:italic>\n                    <\/jats:styled-content>\n                    in patients with\n                    <jats:styled-content style=\"fixed-case\">OAT<\/jats:styled-content>\n                    for the first time, and this research could afford precise genetic diagnosis for the patients. It has broadened the variant spectrum of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>MDC1<\/jats:italic>\n                    <\/jats:styled-content>\n                    , which is conducive to the development of targeted therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1111\/cge.70058","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T05:05:23Z","timestamp":1757999123000},"page":"552-557","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Variants in\n                    <scp>\n                      <i>MDC1<\/i>\n                    <\/scp>\n                    are Associated With Severe Oligoasthenoteratozoospermia"],"prefix":"10.1111","volume":"109","author":[{"given":"Xu","family":"Liu","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology The Second Affiliated Hospital of Anhui Medical University  Hefei Anhui China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University)  Hefei Anhui China"},{"name":"Engineering Research Center of Biopreservation and Artificial Organs Ministry of Education  Hefei Anhui China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University) Ministry of Education of the People's Republic of China  Hefei Anhui China"},{"name":"Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases  Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology The Second Affiliated Hospital of Anhui Medical University  Hefei Anhui China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University)  Hefei Anhui China"},{"name":"Engineering Research Center of Biopreservation and Artificial Organs Ministry of Education  Hefei Anhui China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University) Ministry of Education of the People's Republic of China  Hefei Anhui China"},{"name":"Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases  Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Tan","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Xiangya School of Basic Medical Science Central South University  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hujia","family":"Tan","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology The Second Affiliated Hospital of Anhui Medical University  Hefei Anhui China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University)  Hefei Anhui China"},{"name":"Engineering Research Center of Biopreservation and Artificial Organs Ministry of Education  Hefei Anhui China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University) Ministry of Education of the People's Republic of China  Hefei Anhui China"},{"name":"Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases  Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology The Second Affiliated Hospital of Anhui Medical University  Hefei Anhui China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University)  Hefei Anhui China"},{"name":"Engineering Research Center of Biopreservation and Artificial Organs Ministry of Education  Hefei Anhui China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University) Ministry of Education of the People's Republic of China  Hefei Anhui China"},{"name":"Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases  Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengcheng","family":"Hu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology The Second Affiliated Hospital of Anhui Medical University  Hefei Anhui China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University)  Hefei Anhui China"},{"name":"Engineering Research Center of Biopreservation and Artificial Organs Ministry of Education  Hefei Anhui China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University) Ministry of Education of the People's Republic of China  Hefei Anhui China"},{"name":"Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases  Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunxia","family":"Cao","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University)  Hefei Anhui China"},{"name":"Engineering Research Center of Biopreservation and Artificial Organs Ministry of Education  Hefei Anhui China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University) Ministry of Education of the People's Republic of China  Hefei Anhui China"},{"name":"Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases  Hefei Anhui China"},{"name":"Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center Anhui Medical University  Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengsong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Science Anhui Medical University  Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yichang","family":"Lu","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Reproduction and Genetics in Hunan Province Reproductive and Genetic Hospital of CITIC\u2010Xiangya  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8543-9028","authenticated-orcid":false,"given":"Fuxi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology The Second Affiliated Hospital of Anhui Medical University  Hefei Anhui China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University)  Hefei Anhui China"},{"name":"Engineering Research Center of Biopreservation and Artificial Organs Ministry of Education  Hefei Anhui China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University) Ministry of Education of the People's Republic of China  Hefei Anhui China"},{"name":"Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases  Hefei Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.07.067"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/35056049"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/16.6.1110"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2007.02.011"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deab099"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.11.002"},{"key":"e_1_2_11_8_1","first-page":"378","volume-title":"Toward Reproductive Certainty: Fertility and Genetics Beyond 1999","author":"Gardner D. K. S. W.","year":"1999"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.024"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2004.09.010"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2006.01.012"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.09.038"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500273200"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01445"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01446"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03\u20100310com"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210749200"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010023\u201000624\u20109"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2006.10507096"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70058","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70058","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70058","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T04:34:42Z","timestamp":1770870882000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/cge.70058"],"URL":"https:\/\/doi.org\/10.1111\/cge.70058","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.70058\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70058\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70058\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70058\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70058\/v1\/review2","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,15]]},"assertion":[{"value":"2025-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}