case_images: PMC10623345_01
case_images: Pedigree (A) and timeline of pregnancies (B) in the family.
case_images: fgene-14-1267241-g001.jpg
case_images: PMC10623345_01_fgene-14-1267241-g001.jpg
case_images: F1
case_images: The Chinese couple with five past pregnancies presented to our clinic with a history of recurrent pregnancy loss (Figure 1).
case_images: Ultrasound pictures from the third and fourth pregnancy (fetuses II:3 and II:4). (A) II:3: hydrocephalus. (B) II:3: ascites. (C) II:3: pleural effusion. (D) II:3: polycystic dysplasia of right kidney. (E) II:3: polycystic dysplasia of left kidney. (F) II:3: clubbed right foot. (G) II:3: endocardial cushion defects. (H) II:4: hydranencephaly. (I) II:4: bilateral renal agenesis. Yellow arrows indicate where the anomalies occur.
case_images: fgene-14-1267241-g002.jpg
case_images: PMC10623345_01_fgene-14-1267241-g002.jpg
case_images: F2
case_images: A second trimester ultrasound scan was then performed at GW 21 + 4 and showed that fetus II:3 presented with hydrops, severe hydrocephalus (Figure 2A), ascites (Figure 2B), pleural effusion (Figure 2C), oligohydramnios, polycystic dysplasia of bilateral kidneys (Figures 2D, E), clubfoot (Figure 2F) and endocardial cushion defects (Figure 2G). Figure 2H), anhydramnios (amniotic fluid index: 0 cm) and bilateral renal agenesis (Figure 2I). Face and limbs could not be identified.
case_images: Genetic analysis of the CEP55 variants. (A) Schematic representation of CEP55 protein indicating the position of the disease-associated variants. The region marked in blue (residue 157-236) is tumour suppressor gene 101 (TSG101) and apoptosis-linked gene 2 interacting protein X (ALIX) binding domain. The two variants p.Arg64* and p.Lys70* identified in the current study are highlighted in red. The variants that caused perinatal deaths in previous studies are marked in black. The variants identified in viable cases are marked in gray. (B) Sanger sequencing validation of the two CEP55 variants in the family.
case_images: fgene-14-1267241-g003.jpg
case_images: PMC10623345_01_fgene-14-1267241-g003.jpg
case_images: F3
case_images: TSG101 and ALIX binding domain (Figure 3A). The nonsense CEP55 variant p.Arg64* (ClinVar ID: 1065435) is classified as likely pathogenic in the ClinVar database. This variant in the compound heterozygous state has previously been reported in a case of nonimmune hydrops fetalis (NIHF) with a second missense CEP55 variant p.His458Arg. The nonsense CEP55 variant p.Arg70* is not included in the ClinVar or HGMD databases. Moreover, Sanger sequencing confirmed that both variants were located in trans and segregated with disease in the family (Figure 3B).