[Whole exome sequencing analysis of compound heterozygous variants of CDAN1 gene in a Chinese family with non-immune hydrops fetalis].

OBJECTIVE

To study the clinical characteristics and genetic variants in a family with non-immune hydrops fetalis.

METHODS

Peripheral blood samples were collected from a pregnant woman with suspected non-immune hydrops fetalis of the fetus for routine blood analysis, Rh typing and TORCH test. Amniotic fluid sample was collected for G-banded chromosomal karyotyping. The genomic DNA of the proband was extracted for analysis of chromosomal abnormalities using copy number variation sequencing. Whole-exome sequencing (Trios-WES) was performed on Illumina NovaSeq 6000 platform and exonic DNA was enriched using Agilent Sure Select XT Human All Exon V6. Sorting intolerant from tolerant (SIFT), I-mutant2, PolyPhen-2 and PROVEAN were used to predict the potential effects of amino acid substitution on protein function and splicing variation. The spatial structure of codanin-1 was modeled and visualized with Alpha Fold 2 and PyMOL 2.3 software, and the variants with potential clinical significance were confirmed by Sanger sequencing.

RESULTS

Fetal ultrasound at 17 weeks of gestation showed extensive subcutaneous edema, ascites, pleural effusion, enlarged liver and spleen, thickened placenta and pericardium defect. NGS reveals that proband has carried c.2140C>T, p.R714W, and c.1264_1265delCT, p.L422* compound heterozygous variants of CDAN1 gene, which were found to be pathogenic and inherited from proband's father and mother respectively.

CONCLUSION

We identified a novel heterozygous CDAN1 gene mutation causing fetal-onset congenital dyserythropoietic anemia type 1, which triggers non-immune hydrops fetalis.