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

Yeping Wang; Fang Sheng; Lingjing Ying; Qiaoli Lou; Zhaonan Yu; Kaixuan Wang; Haoyi Wang

doi:10.3389/fgene.2023.1267241

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

Front Genet. 2023 Oct 20:14:1267241. doi: 10.3389/fgene.2023.1267241. eCollection 2023.

Authors

Yeping Wang^{1

2}, Fang Sheng¹, Lingjing Ying², Qiaoli Lou³, Zhaonan Yu^{4

5}, Kaixuan Wang², Haoyi Wang^{5

6}

Affiliations

¹ Jinhua Maternity and Child Health Care Hospital, Jinhua, China.
² Jinhua Municipal Central Hospital, Jinhua, China.
³ Wuyi County First People's Hospital, Jinhua, China.
⁴ Medical School of Tianjin University, Tianjin, China.
⁵ Hangzhou D. A. Medical Laboratory, Hangzhou, China.
⁶ Precision Diagnosis and Treatment Center of Jinhua City, Jinhua, China.

Abstract

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

Keywords: CEP55; Meckel syndrome; case report; fetal loss; stillbirth.

Publication types

Case Reports

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Key social development projects of the Jinhua science and technology plan project, Grant No. 2022-3-128; Research and cultivation fund project of the Jinhua Maternity and Child Healthcare Hospital, Grant No. JHFB 2021-2-03.