{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T15:02:28Z","timestamp":1785078148637,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Isolated hypogonadotropic hypogonadism (IHH) is a rare endocrine disorder caused by genes such as\n                      <jats:italic>ANOSI (OMIM*300836), FGFR1 (OMIM*136350), PROK2 (OMIM*607002)<\/jats:italic>\n                      and\n                      <jats:italic>PROKR2 (OMIM*607123)<\/jats:italic>\n                      (etc.), leading to downstream dysfunction of pituitary gonadotropin secretion and subsequent impairment of gonadal function. Clinical manifestations include incomplete or partial puberty and infertility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      In this study, whole\u2010genome sequencing of a female patient with HH identified a novel 5\u2032 splice site variant c.285\u2009+\u2009772\u2009T&gt;G in the deep intron of\n                      <jats:italic>PROK2<\/jats:italic>\n                      (NM_001126128.2). In\u00a0vitro minigene validation revealed abnormal splicing of this variant, with 69 base pairs retained in intron 3, ultimately leading to changes in protein length, which may lead to changes in protein structure. According to the American College of Medical Genetics and Genomics (ACMG) pathogenicity classification, this variant is rated as likely pathogenic variant (LP).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>PROK2<\/jats:italic>\n                      variants can lead to HH and we report a case with a novel splice site variant that has been confirmed to lead to the retention of 69 base pairs in intron 3 during RNA splicing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70267","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:31:46Z","timestamp":1784089906000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Pathogenicity Analysis of a Hypogonadotropic Hypogonadism Patient With the Novel Variant in the Deep Intronic Region of the\n                    <scp>\n                      <i>PROK2<\/i>\n                    <\/scp>\n                    Gene"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3704-9404","authenticated-orcid":false,"given":"Jiali","family":"Chen","sequence":"first","affiliation":[{"name":"Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Key Laboratory of Hereditary Rare Diseases of Health Commission of Henan Province, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology  Luoyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2054-3398","authenticated-orcid":false,"given":"Yujin","family":"Ma","sequence":"additional","affiliation":[{"name":"Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Key Laboratory of Hereditary Rare Diseases of Health Commission of Henan Province, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology  Luoyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7396-1310","authenticated-orcid":false,"given":"Liping","family":"Li","sequence":"additional","affiliation":[{"name":"Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Key Laboratory of Hereditary Rare Diseases of Health Commission of Henan Province, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology  Luoyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2738-2080","authenticated-orcid":false,"given":"Huifang","family":"Peng","sequence":"additional","affiliation":[{"name":"Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Key Laboratory of Hereditary Rare Diseases of Health Commission of Henan Province, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology  Luoyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3807-7989","authenticated-orcid":false,"given":"Hongwei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Key Laboratory of Hereditary Rare Diseases of Health Commission of Henan Province, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology  Luoyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0958"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01087-x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0911064"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-022-00940-8"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/417405a"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2654"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020175"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac615"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-020-01248-y"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2025.102000"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep32819"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.15"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn2479"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-022-00940-9"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1132787"},{"issue":"10","key":"e_1_2_12_17_1","article-title":"Prokineticin 2\/PROK2 and Male Infertility","volume":"10","author":"Petrella C.","year":"2022","journal-title":"Biomedicine"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2024.112224"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-46883-6"},{"issue":"2","key":"e_1_2_12_20_1","article-title":"Whole Genome Sequencing for USH2A\u2010Associated Disease Reveals Several Pathogenic Deep\u2010Intronic Variants That Are Amenable to Splice Correction","volume":"4","author":"Reurink J.","year":"2023","journal-title":"HGG Adv"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009622107"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1809-4"},{"key":"e_1_2_12_24_1","volume-title":"International Statistical Classification of Diseases, 11th Revision","author":"World Health Organization","year":"2019"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11496"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70267","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.70267","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70267","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T14:50:07Z","timestamp":1785077407000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":24,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/mgg3.70267"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70267","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-01-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70267"}}