{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:07:00Z","timestamp":1788941220538,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":251,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Cornelia de Lange syndrome (CdLS) currently has seven known causative genes, inherited in an autosomal or X\u2010linked dominant pattern. Clinical features are variable, including dysmorphic facial features, intrauterine and\/or postnatal growth retardation, multiple organ system malformations, and neurodevelopmental disorders. Type 4 of CdLS caused by\n                      <jats:italic>RAD21<\/jats:italic>\n                      gene has a relatively mild phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we report a pair of siblings from a Chinese family who both have similar dysmorphic facial features, cleft palate, spina bifida occulta, and limb phenotypes. Whole\u2010genome sequencing (WGS) was performed to analyze the genetic basis of their condition. Gap\u2010PCR was subsequently employed to map the breakpoints in the affected siblings\u2032 peripheral blood samples. Additionally, the copy number status of the parents and the father\u2032s sperm DNA were evaluated using Gap\u2010PCR and digital PCR (dPCR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Through WGS analysis, a heterozygous deletion was found in the 8q23.3\u20108q24.11 region of both patients, which includes the full\u2010length\n                      <jats:italic>RAD21<\/jats:italic>\n                      gene. And we mapped the breakpoint with the peripheral blood samples of the affected siblings using Gap\u2010PCR. The parents\u2032 peripheral blood had normal copy number. The father\u2032s sperm DNA was negative for the deletion by both Gap\u2010PCR and dPCR, whereas the mother\u2032s peripheral blood was also negative, suggesting the deletion is likely due to maternal gonadal mosaicism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We report a pair of siblings with a complete loss of\n                      <jats:italic>RAD21<\/jats:italic>\n                      , with evidence supporting maternal gonadal mosaicism. This information will be helpful for genetic counseling for Type 4 of CdLS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/5591607","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T07:36:55Z","timestamp":1788939415000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["First Cornelia de Lange Syndrome Type 4 Caused by the Gonadal Mosaicism of\n                    <i>RAD21<\/i>\n                    Deletion"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4359-1060","authenticated-orcid":false,"given":"Yanchuan","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5483-1677","authenticated-orcid":false,"given":"Dongyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2914-3792","authenticated-orcid":false,"given":"Wensheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2765-7088","authenticated-orcid":false,"given":"Yingjie","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3707-1221","authenticated-orcid":false,"given":"Li","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7396-1310","authenticated-orcid":false,"given":"Liping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1211-1969","authenticated-orcid":false,"given":"Guangda","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3807-7989","authenticated-orcid":false,"given":"Hongwei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0031-0"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy329"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes14122212"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes14010119"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.0466"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.4.749"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012112"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102573"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-018-1004-3"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30137"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.04.019"},{"key":"e_1_2_13_12_2","doi-asserted-by":"crossref","first-page":"973","DOI":"10.4161\/epi.28903","article-title":"Overall and Allele-Specific Expression of the SMC1A Gene in Female Cornelia De Lange Syndrome Patients and Healthy Controls","volume":"9","author":"Parenti I.","year":"2014","journal-title":"Epigenetics"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0085-6"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.16288\/j.yczz.19-288"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.774950"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-020-0754-6"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-022-02517-x"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1017002221520"}],"container-title":["Human 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