AUTHOR=Wang Yeping , Sheng Fang , Ying Lingjing , Lou Qiaoli , Yu Zhaonan , Wang Kaixuan , Wang Haoyi 

TITLE=CEP55-associated lethal fetal syndrome: a case report of a Chinese family

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1267241

DOI=10.3389/fgene.2023.1267241

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Research on fetal loss related to germline mutations in single genes remains limited. Disruption of <italic>CEP55</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 <italic>CEP55</italic> variants.</p><p><bold>Case presentations:</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 <italic>CEP55</italic> variants comprised of c.190C&gt;T(p.Arg64*) and c.208A&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.</p><p><bold>Conclusion:</bold> This is the fifth reported family wherein biallelic <italic>CEP55</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 <italic>CEP55</italic>-associated lethal fetal syndrome, highlighting the vital biomolecular function of CEP55.</p>