Identification of novel biallelic mutations in CFAP53 associated with fetal situs inversus totalis and literature review.

Visceral heterotaxy is a congenital malformation characterized by the abnormal arrangement of left-right axis of visceral organs. To date, several genes implicated in the regulation of laterality patterning have been identified. Notably, CFAP53, also referred to as CCDC11, is involved in the regulation of ciliary motility, and mutations in this gene have been linked to a rare condition of heterotaxy. In this study, whole-exome sequencing (WES) was utilized to analyze the genetic causes of a fetus in a Chinese family, presenting with situs inversus totalis. In silico predictions and functional studies were performed to evaluate the pathogenicity of the identified candidate gene variants. WES revealed two novel compound heterozygous mutations, c.777G > T and c.1013A > T, in the CFAP53 gene. Minigene experiments demonstrated that c.777G > T may result in splicing aberrations, thus leading to the production of truncated CFAP53 proteins. Additionally, in silico analyses indicate that c.1013A > T could disrupt the interaction between CFAP53 and its target protein, TTC25. We report the second documented case of fetus with situs inversus totalis due to biallelic loss-of-function variants in CFAP53. According to literature review, our findings provide a basis for the prenatal diagnosis and genetic counseling of CFAP53 mutation-associated visceral heterotaxy.