A novel homozygous missense variant in BTG4 causes zygotic cleavage failure and female infertility

Purpose Zygotic cleavage failure is an embryonic phenotype that causes female infertility and failure of in vitro fertilization and/or intracytoplasmic sperm injection. We aimed to identify pathogenic variants in a female infertility patient from a consanguineous family with the zygotic cleavage failure phenotype. Methods Whole-exome sequencing was performed in the affected patient; Sanger sequencing was used to confirm the identified variant. The functional effect of the identified variant was further investigated in HeLa cells. Results We identified a novel homozygous missense mutation in BTG4 (c.285G > C, p.W95C) in the affected individual. Co-immunoprecipitation in HeLa cells showed the complete loss of the interaction between the p.W95C BTG4 variant protein and CNOT7. Conclusion This study confirms our previous research and expands the mutational spectrum of BTG4. Our findings complement the diagnostic genetic basis for zygotic cleavage failure patients and suggest that BTG4 may be a good target for future therapeutic strategies.

Automated summary

This study identified a novel homozygous missense mutation in the BTG4 gene in a female infertility patient with zygotic cleavage failure phenotype, and demonstrated its functional effect on protein interaction in HeLa cells. These findings expand the mutational spectrum of BTG4 and suggest its potential as a therapeutic target for zygotic cleavage failure patients.