{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T07:32:03Z","timestamp":1788939123526,"version":"build-2803163510"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T00:00:00Z","timestamp":1697760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Research on fetal loss related to germline mutations in single genes remains limited. Disruption of <jats:italic>CEP55<\/jats:italic> has recently been established in association with perinatal deaths characterized by hydranencephaly, renal dysplasia, oligohydramnios, and characteristic dysmorphisms. We herein present a Chinese family with recurrent fetal losses due to compound heterozygous nonsense <jats:italic>CEP55<\/jats:italic> variants.<\/jats:p><jats:p><jats:bold>Case presentations:<\/jats:bold> The Chinese couple had a history of five pregnancies, with four of them proceeding abnormally. Two stillbirths (II:3 and II:4) sequentially occurred in the third and fourth pregnancy. Prenatal ultrasound scans revealed phenotypic similarities between fetuses II:3 and II:4, including oligohydramnios, bilateral renal dysplasia and hydrocephalus\/hydranencephaly. Clubfoot and syndactyly were also present in both stillborn babies. Fetus II:3 presented with endocardial cushion defects while fetus II:4 did not. With the product of conception in the fourth pregnancy, whole exome sequencing (WES) on fetus II:4 identified compound heterozygous nonsense <jats:italic>CEP55<\/jats:italic> variants comprised of c.190C&amp;gt;T(p.Arg64*) and c.208A&amp;gt;T(p.Lys70*). Both variants were expected to result in lack of the TSG101 and ALIX binding domain. Sanger sequencing confirmed the presence and cosegregation of both variants.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This is the fifth reported family wherein biallelic <jats:italic>CEP55<\/jats:italic> variants lead to multiple perinatal deaths. Our findings, taken together with previously described phenotypically similar cases and even those with a milder and viable phenotype, broaden the genotypic and phenotypic spectrum of <jats:italic>CEP55<\/jats:italic>-associated lethal fetal syndrome, highlighting the vital biomolecular function of CEP55.<\/jats:p>","DOI":"10.3389\/fgene.2023.1267241","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T13:12:19Z","timestamp":1697807539000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["CEP55-associated lethal fetal syndrome: a case report of a Chinese family"],"prefix":"10.3389","volume":"14","author":[{"given":"Yeping","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjing","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoli","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaonan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1038\/ejhg.2014.174","article-title":"Meckel-Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe","volume":"23","author":"Barisic","year":"2015","journal-title":"Eur. 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