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The structural stability of the WBP11 protein associated with missense variants was characterized using 3D protein structural modeling. The impact of splicing variant was further evaluated through TA cloning coupled with Sanger sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Here, we report the first case series of\n                      <jats:italic>WBP11<\/jats:italic>\n                      -related disorder in Chinese patients, comprising four fetuses and one postnatal child from five unrelated families. Whole-exome sequencing identified five previously unreported heterozygous\n                      <jats:italic>WBP11<\/jats:italic>\n                      variants (NM_016312.3), including three nonsense (p.Arg55*, p.Lys83*, p.Ser279*), one canonical splice-site (c.1310-1G\u2009&gt;\u2009A), and one missense (p.Arg91Cys). Three occurred de novo, while two were paternally inherited from clinically unaffected or mildly affected carriers, supporting incomplete penetrance. Crucially, RNA analysis of amniocytes carrying the c.1310-1G\u2009&gt;\u2009A variant revealed only 4% aberrant splicing (c.1310del, p.Gly437Glufs*6), explaining the mild fetal phenotype of isolated femoral shortening and challenging conventional assumptions about the pathogenicity of canonical splice-site variants. The postnatal patient primarily presents with retinal pigmentary degeneration, hearing impairment, bilateral cryptorchidism, short stature, and global developmental delay. Most of these features have been reported in\n                      <jats:italic>WBP11<\/jats:italic>\n                      -related cases but are not considered classic diagnostic criteria for VACTERL. Notably, prenatal cases predominantly presented with cardiac malformations, whereas vertebral anomalies, common postnatally, were absent prenatally, suggesting age-dependent phenotypic evolution.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We have documented the retinal pigment phenotype in\n                      <jats:italic>WBP11<\/jats:italic>\n                      mutant patients for the first time. Our findings expand the mutational and clinical spectrum of\n                      <jats:italic>WBP11<\/jats:italic>\n                      -related disease, highlight the limitations of sequence-based variant interpretation without functional or transcriptomic validation, and underscore the necessity of integrating detailed phenotypic correlation into prenatal genetic counseling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40246-026-00966-3","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T20:54:45Z","timestamp":1776113685000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal and postnatal manifestations of WBP11-related disorder in Chinese patients: expanding the phenotypic and mutational spectrum"],"prefix":"10.1186","volume":"20","author":[{"given":"Tingbin","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoying","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyi","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"issue":"Pt 1","key":"966_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1042\/bj20030950","volume":"378","author":"M Llorian","year":"2004","unstructured":"Llorian M, Beullens M, Andres I, Ortiz JM, Bollen M. 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