{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:10:29Z","timestamp":1784005829808,"version":"3.55.0"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> Patients with syndromic 46, XY disorders\/differences of sex development (DSD) are characterized by gonadal and phenotypic genders inconsistent with their chromosomal sexes as well as abnormalities of multiple extragonadal organs. They are caused by mutations in specific genes, which are expressed in the affected organs and regulate their development, and over fourteen genes have been identified. In this study, we aimed to determine the underlying cause of a patient with syndromic 46, XY DSD and review the clinical presentations and genetic findings of all reported similar cases.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Whole-exome sequencing (WES) was performed to find a molecular cause of the patient. <jats:italic>In silico<\/jats:italic> tools were used to analyze the pathogenicity of the variants. Reports of cases with similar clinical features and involved genes were summarized by searching through PubMed\/MEDLINE using keywords \u201c<jats:italic>PPP2R3C<\/jats:italic>\u201d or \u201c<jats:italic>G5PR<\/jats:italic>\u201d and \u201c46,XY disorders of sex development\u201d.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Compound heterozygous variants (p.F229del\/p.G417E) in <jats:italic>PPP2R3C<\/jats:italic> were identified in the 24-year-old female by WES and verified by Sanger sequencing. The patient presents complete testicular dysgenesis, low birth weight, facial deformity, cubitus valgus, and decreasing number of CD19<jats:sup>+<\/jats:sup> B lymphocytes and CD4<jats:sup>+<\/jats:sup> T lymphocytes. A total of thirteen 46, XY DSD cases with four homozygous <jats:italic>PPP2R3C<\/jats:italic> mutations (p.Leu103Pro, p.Leu193Ser, p.Phe350Ser, and p.Ser216_Tyr218dup) have been reported previously, and their clinical manifestations are roughly similar to those of our patient.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Novel compound heterozygous variants in <jats:italic>PPP2R3C<\/jats:italic> cause specific syndromic 46, XY gonadal dysgenesis, which broadened the pathogenic variants spectrum of <jats:italic>PPP2R3C<\/jats:italic>. The typical phenotype of <jats:italic>PPP2R3C<\/jats:italic> mutation is complete 46, XY gonadal dysgenesis with multiple extragonadal anomalies, including facial deformities, skeletal system abnormalities, muscle abnormalities, impaired nervous system, impaired hearing and vision, heart and kidney anomalies, and gastrointestinal dysfunction.<\/jats:p>","DOI":"10.3389\/fgene.2022.871328","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T06:17:00Z","timestamp":1655965020000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Case Report: Novel Compound Heterozygotic Variants in PPP2R3C Gene Causing Syndromic 46, XY Gonadal Dysgenesis and Literature Review"],"prefix":"10.3389","volume":"13","author":[{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangfeng","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1111\/cge.14086","article-title":"Expanding the Spectrum of Syndromic PPP2R3C \u2010Related XY Gonadal Dysgenesis to XX Gonadal Dysgenesis","volume":"101","author":"Altunoglu","year":"2022","journal-title":"Clin. 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Androl."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.871328\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T06:17:03Z","timestamp":1655965023000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.871328\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,23]]},"references-count":12,"alternative-id":["10.3389\/fgene.2022.871328"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.871328","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,23]]},"article-number":"871328"}}