A novel homozygous C-terminal deletion in BTG4 causes zygotic cleavage failure and female infertility

This study conforms previous studies and expands the mutational spectrum of BTG4. Our findings prove the functional importance of the C-terminal of BTG4. BTG4 is a potential diagnostic and therapeutic target for patients suffering from zygotic cleavage failure.

The genomic DNA from the affected individual was subjected to whole-exome sequencing and the variant was confirmed by Sanger sequencing. The functional effect of the identified variant was further investigated in 293 T cells.

We aimed to identify pathogenic variants in a female patient with primary infertility and recurrent failure of in vitro fertilization with zygotic cleavage failure.

We identified a novel homozygous deletion in BTG4 (c.580_616del) in the affected individual. The deletion results in frameshift and replacement of the last 29 residues (aa195-223) with 66 random amino acids. The mutated amino acid residues are highly conserved among mammalian species. Co-immunoprecipitation in 293 T cells showed that the mutation abolished the interaction between BTG4 and PABPN1L.