Case Report: A case of Fraser syndrome 2 in a Chinese fetus caused by novel compound heterozygous variants in the FREM2 gene.

Background: Fraser syndrome (FS) is an autosomal recessive inherited malformation disorder characterized by cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tracts. Variants in the FRAS1-related extracellular matrix 2 (FREM2) gene are the major genetic cause. However, clinical diagnosis remains challenging due to phenotypic heterogeneity. Methods: A 24-week pregnant woman came to our hospital for genetic diagnosis. Ultrasound examination showed bilateral renal agenesis or dysplasia, absence of the bladder, and almost oligohydramnios. Trio whole-exome sequencing (Trio-WES) identified two novel compound heterozygous variants in the fetal FREM2 gene: a maternal, frameshift variant, c.5908_5909del, p.Leu1970ValfsTer33, and a paternal, nonsense variant, c.7881C>G,p.Tyr2627Ter. Conclusion: We report a rare case of Fraser syndrome 2 caused by compound heterozygous mutations in the FREM2 gene. Our findings expanded the FREM2 genotypic spectrum and demonstrated the significance of Trio-WES in the prenatal diagnosis of recessive disorders.