{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:09:58Z","timestamp":1784005798471,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Homozygous variants in\n                    <jats:italic>PPP2R3C<\/jats:italic>\n                    have been reported to cause a syndromic 46,XY complete gonadal dysgenesis phenotype with extragonadal manifestations (GDRM, MIM# 618419) in patients from four unrelated families, whereas heterozygous variants have been linked to reduced fertility with teratozoospermia (SPGF36, MIM# 618420) in male carriers. We present eight patients from four unrelated families of Turkish and Indian descent with three different germline homozygous\n                    <jats:italic>PPP2R3C<\/jats:italic>\n                    variants including a novel in\u2010frame duplication (c.639_647dupTTTCTACTC, p.Ser216_Tyr218dup). All patients exhibit recognizable facial dysmorphisms allowing gestalt diagnosis. In two 46,XX patients with hypergonadotropic hypogonadism and nonvisualized gonads, primary amenorrhea along with absence of secondary sexual characteristics and\/or unique facial gestalt led to the diagnosis. 46,XY affected individuals displayed a spectrum of external genital phenotypes from ambiguous genitalia to complete female. We expand the spectrum of syndromic\n                    <jats:italic>PPP2R3C<\/jats:italic>\n                    \u2010related XY gonadal dysgenesis to both XY and XX gonadal dysgenesis. Our findings supported neither ocular nor muscular involvement as major criteria of the syndrome. We also did not encounter infertility problems in the carriers. Since both XX and XY individuals were affected, we hypothesize that\n                    <jats:italic>PPP2R3C<\/jats:italic>\n                    is essential in the early signaling cascades controlling sex determination in humans.\n                  <\/jats:p>","DOI":"10.1111\/cge.14086","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T22:24:05Z","timestamp":1636410245000},"page":"221-232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Expanding the spectrum of syndromic\n                    <i>PPP2R3C<\/i>\n                    \u2010related\n                    <scp>XY<\/scp>\n                    gonadal dysgenesis to\n                    <scp>XX<\/scp>\n                    gonadal dysgenesis"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3172-5368","authenticated-orcid":false,"given":"Umut","family":"Altunoglu","sequence":"first","affiliation":[{"name":"Medical Genetics Department Ko\u00e7 University School of Medicine (KUSoM) and Hospital  Istanbul Turkey"},{"name":"Medical Genetics Department Istanbul University Istanbul Medical School  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1326-0608","authenticated-orcid":false,"given":"Esra","family":"B\u00f6rkl\u00fc","sequence":"additional","affiliation":[{"name":"Medical Genetics Department Ko\u00e7 University School of Medicine (KUSoM) and Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2471-4094","authenticated-orcid":false,"given":"Anju","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of Higher Education  Manipal Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7706-1608","authenticated-orcid":false,"given":"Nathalie","family":"Escande\u2010Beillard","sequence":"additional","affiliation":[{"name":"Medical Genetics Department Ko\u00e7 University School of Medicine (KUSoM) and Hospital  Istanbul Turkey"},{"name":"Institute of Medical Biology A*STAR  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Ledig","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik Westfaelische Wilhelms\u2014Universitaet Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00fclya","family":"Azakl\u0131","sequence":"additional","affiliation":[{"name":"Medical Genetics Department Ko\u00e7 University School of Medicine (KUSoM) and Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini S.","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of Higher Education  Manipal Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7674-7384","authenticated-orcid":false,"given":"Serpil","family":"Eraslan","sequence":"additional","affiliation":[{"name":"Medical Genetics Department Ko\u00e7 University School of Medicine (KUSoM) and Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-8239","authenticated-orcid":false,"given":"Katta Mohan","family":"Girisha","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of Higher Education  Manipal Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Kennerknecht","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik Westfaelische Wilhelms\u2014Universitaet Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0376-499X","authenticated-orcid":false,"given":"H\u00fclya","family":"Kayserili","sequence":"additional","affiliation":[{"name":"Medical Genetics Department Ko\u00e7 University School of Medicine (KUSoM) and Hospital  Istanbul Turkey"},{"name":"Medical Genetics Department Istanbul University Istanbul Medical School  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000332209"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2019.04.005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000448667"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(80)80013-8"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320260111"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320590114"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.9.759"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.151"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000444065"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-18-0256"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-19-0067"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_14_1","unstructured":"EllardS BapleEL CallawayA et al.Association for Clinical Genetic Science consensus statement on adoption of the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant classification and interpretation [press release];2016.http:\/\/www.acgs.uk.com\/media\/1032817\/acgs_consensus_statement_on_adoption_of_acmg_guidelines__1_pdf"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320470807"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1384"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0251608"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2012-0101-RS"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050637"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.10.028"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00169-12"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.2002.00562.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000326815"},{"issue":"11","key":"e_1_2_8_24_1","first-page":"3850","article-title":"An inactivating mutation of the luteinizing hormone receptor causes amenorrhea in a 46,XX female","volume":"81","author":"Toledo SPA","year":"1996","journal-title":"J Clin Endocr Metab"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2019.01.004"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204455200"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502464200"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.08.010"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.12.013"},{"issue":"4","key":"e_1_2_8_30_1","first-page":"2835","article-title":"MicroRNA\u2010139\u20105p elevates skeletal myogenic differentiation of human adult dental pulp stem cells through Wnt\/beta\u2010catenin signaling pathway","volume":"16","author":"Xie Y","year":"2018","journal-title":"Exp Ther Med"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes9030121"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.030015"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1159\/000277140"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-00482"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14086","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.14086","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14086","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T07:18:10Z","timestamp":1693207090000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,17]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1111\/cge.14086"],"URL":"https:\/\/doi.org\/10.1111\/cge.14086","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14086\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14086\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14086\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14086\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14086\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14086\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,17]]},"assertion":[{"value":"2021-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}