{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:08:36Z","timestamp":1779512916264,"version":"3.53.1"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"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;amp; Gen Med"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Ornithine transcarbamylase deficiency (OTCD, MIM#311250) is a rare X\u2010linked urea cycle disorder causing hyperammonemia. While around 600 pathogenic\n                      <jats:italic>OTC<\/jats:italic>\n                      variants have been reported, cryptic changes like synonymous or in\u2010frame variants remain poorly characterized and are easily overlooked in routine screening.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed the clinical and genetic profiles of two unrelated Chinese male patients clinically diagnosed with OTCD. Whole\u2010exome sequencing (WES) was performed to identify the genetic etiology. A minigene assay was then used to assess the splicing effect of the detected synonymous variant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WES revealed two rare\n                      <jats:italic>OTC<\/jats:italic>\n                      variants: a synonymous variant (NM_000531.6: c.663G&gt;A, p.Lys221Lys) and a novel\n                      <jats:italic>de novo<\/jats:italic>\n                      inframe variant (c.756_761dupAGCAGC, p.Ala253_Ala254dup). Minigene assay confirmed that the c.663G&gt;A variant causes exon 6 skipping, leading to the deletion of 41 amino acids (c.541_663del, p.Glu181_Lys221del). Both variants were classified as clinically pathogenic, and the genotype\u2013phenotype relationships were potentially established.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study expands the mutation spectrum of\n                      <jats:italic>OTC<\/jats:italic>\n                      and emphasizes the importance of cryptic variants interpretation and the need for additional functional studies to verify the pathogenicity of these variants.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70223","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:38:51Z","timestamp":1777437531000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pedigree and Functional Analysis of Two Cryptic\n                    <i>OTC<\/i>\n                    Variants Causing Ornithine Transcarbamylase Deficiency in Two Unrelated Chinese Male Patients"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7053-305X","authenticated-orcid":false,"given":"Qingming","family":"Wang","sequence":"first","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Xiao","sequence":"additional","affiliation":[{"name":"The Sixth Affiliated Hospital Guangdong Pharmaceutical University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Huadu District People's Hospital of Guangzhou  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Huadu District People's Hospital of Guangzhou  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8510-0419","authenticated-orcid":false,"given":"Haiming","family":"Yuan","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010015\u20109901\u20101"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2015.04.003"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380110128"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62031"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2020.100598"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.12457"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12100"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6372096"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010020\u201001606\u20102"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2020.12.003"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.22.110801.140547"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010017\u20100661\u2010x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12031"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098\u20101004(1996)8:4<373::AID\u2010HUMU13>3.0.CO;2"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380110103"},{"key":"e_1_2_12_18_1","volume-title":"GeneReviews [Internet]","author":"Simpson K. 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