{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:33:41Z","timestamp":1790494421956,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003454","name":"Guangxi Zhuang Region Health Department","doi-asserted-by":"publisher","award":["Z20190311"],"award-info":[{"award-number":["Z20190311"]}],"id":[{"id":"10.13039\/501100003454","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003454","name":"Guangxi Zhuang Region Health Department","doi-asserted-by":"publisher","award":["Z20200691"],"award-info":[{"award-number":["Z20200691"]}],"id":[{"id":"10.13039\/501100003454","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003454","name":"Guangxi Zhuang Region Health Department","doi-asserted-by":"publisher","award":["Z20200623"],"award-info":[{"award-number":["Z20200623"]}],"id":[{"id":"10.13039\/501100003454","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital hydrocephalus\u20103 with brain anomalies (HYC3, MIM 617967) is a rare form of congenital hydrocephalus characterized by severe hydrocephalus and cerebellar abnormalities, the onset of the disease occurs in utero even resulting in fetal death. A very limited spectrum of <jats:italic>WDR81<\/jats:italic> pathogenic variants had been reported in three unrelated families with HYC3. This study aims at presenting novel compound heterozygous frameshift variants in <jats:italic>WDR81<\/jats:italic> in a Chinese fetus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing (WES) was performed for a fetus with multiple congenital anomalies including sever hydrocephalus, cleft lip and palate, hydrops fetalis, hepatomegaly, and cerebellar hypoplasia. Sanger sequencing was performed to confirm the origin of the variants subsequently. Variants classification was based on the American College of Medical Genetics and Genomics\/Association for Molecular Pathology (ACMG\/AMP) guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two novel heterozygous variants c.146_147insG (p.Thr52fs) and c.673delC (p.Leu225fs) in <jats:italic>WDR81<\/jats:italic> were identified. Sanger sequencing revealed that the c.146_147insG mutation was maternal origin and the c.673delC mutation was paternal origin. Both variants were pathogenic according to the ACMG\/AMP guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present study expands the mutation spectrum of <jats:italic>WDR81<\/jats:italic> and help further define the genotype\u2013phenotype correlations of HYC3. <jats:italic>WDR81<\/jats:italic>\u2010related HYC3 were highly clinical heterogeneity. We suggested that fetal hydrocephalus with extracerebral manifestations may be suggestive of <jats:italic>WDR81<\/jats:italic> deficiency and WES is effective for achieving a conclusive diagnosis for disorder.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1624","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T12:49:37Z","timestamp":1615898977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel compound heterozygous frameshift variants in <i>WDR81<\/i> associated with congenital hydrocephalus 3 with brain anomalies: First Chinese prenatal case confirms <i>WDR81<\/i> involvement"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1944-8441","authenticated-orcid":false,"given":"Jiasun","family":"Su","sequence":"first","affiliation":[{"name":"Guangxi Health Commission Key Laboratory of Precise Diagnosis and Treatment of Genetic Diseases 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