{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:21:45Z","timestamp":1790814105885,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Genitourinary and\/or brain malformation syndrome (GUBS) is a recently discovered syndrome involving abnormalities of the neurological or urogenital system. <jats:italic>PPP1R12A<\/jats:italic> may be the pathological gene causing this syndrome. Currently, to our knowledge, there is only one study related to GUBS in the world. Here, we report a clinical case of a Chinese newborn with congenital micropenis caused by a non\u2010coding sequence pathogenic variant of <jats:italic>PPP1R12A<\/jats:italic>, providing additional evidence on genetic causes of genital malformation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The genetic cause of the patient's malformation was detected using trio\u2010whole exome sequencing and Sanger sequencing, and reverse transcription\u2010PCR analysis was performed by constructing the minigene mutant plasmid in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic testing revealed a novel heterozygous variant, c.2666+3A&gt;G, of the <jats:italic>PPP1R12A<\/jats:italic> gene of the patient. The parents at this site were wild\u2010type, indicating that this might be a de novo variant. The minigene experiment showed that the c.2666+3A&gt;G plasmid led to the deletion of 17\u2009bp in exon 20, and a new mRNA product c.2650_2666del (p.Thr884IleTer2) with skipping of exon 20 was produced. This may lead to <jats:italic>PPP1R12A<\/jats:italic> haploinsufficiency and cause biological harm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>To our knowledge, this is the first clinical study on a rare variant of <jats:italic>PPP1R12A<\/jats:italic> in the Chinese population. The c.2666+3A&gt;G may lead to external genitalia malformation, such as congenital micropenis in male neonates. The results of this study further verified the correlation between GUBS and <jats:italic>PPP1R12A<\/jats:italic> haploinsufficiency and revealed the important role of a non\u2010coding sequence variant in the pathogenesis of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2223","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T02:01:54Z","timestamp":1686103314000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Clinical report and genetic analysis of a neonate with genitourinary and\/or brain malformation syndrome caused by a non\u2010coding sequence variant of <scp><i>PPP1R12A<\/i><\/scp>"],"prefix":"10.1002","volume":"11","author":[{"given":"Yanxia","family":"Diao","sequence":"first","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Bengbu Medical College  Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Chigene Translational Medicine Research Center Co., Ltd  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Bengbu Medical College  Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Bengbu Medical College  Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0528-7499","authenticated-orcid":false,"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Bengbu Medical College  Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.050106.093909"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2011.01.018"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743\u20106109.2010.02084.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400018200"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.12.004"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2018.07.023"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.06.092"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.143966"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2005.11.001"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352\u20104642(18)30139\u20101"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deac239"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61525"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.074773"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1030119"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0360514"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2223","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T08:39:19Z","timestamp":1697099959000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,5]]},"references-count":16,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1002\/mgg3.2223"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2223","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,5]]},"assertion":[{"value":"2022-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2223"}}