TUBB8 Mutations Cause Female Infertility with Large Polar Body Oocyte and Fertilization Failure

Tubulin beta 8 class VIII (TUBB8) is a special beta-tubulin isotype that mainly expressed in primate oocytes and early embryos and identified as the disease-causing gene of human oocyte maturation arrest. To identify the disease-causing genes in 2 patients with female infertility due to large polar body oocyte or fertilization failure, whole-exome sequencing was performed on the patients and available family members. We identified a novel heterozygous missense mutation c.817C>G (p.L273V) and a recently reported heterozygous missense mutation c.608A>G (p.D203G) in TUBB8 from two patients, respectively. We found oocyte with a large polar body in the patient who carried the p.D203G mutation in TUBB8. Bioinformatics analysis showed that these two mutations are harmful. The results of western blot and RT-PCR experiments showed that the D203G mutation caused a significant decrease in the expression of TUBB8, and immunostaining showed that the TUBB8 mutation caused abnormal microtubule morphology. These findings suggest that TUBB8 mutations resulted in oocyte with a large polar body and fertilization failure in patients.

Automated summary

The study identified two heterozygous missense mutations in the TUBB8 gene that resulted in oocytes with large polar bodies and fertilization failure in two patients. Bioinformatics analysis showed that these mutations are harmful.