A novel compound heterozygous mutation in TUBB8 causing early embryonic developmental arrest

Area of Science:

• Genetics
• Cell Biology
• Reproductive Medicine

Background:

• Mutations in the beta-tubulin isotype, TUBB8, are linked to female infertility.
• The full spectrum of TUBB8 mutations and their impact on reproductive health requires further investigation.

Purpose of the Study:

• To identify novel variants in the TUBB8 gene.
• To investigate the phenotypic effects of these variants on microtubule network structure in vitro.

Main Methods:

• Whole-exome sequencing and Sanger sequencing were used to detect TUBB8 variants in two infertile families.
• In silico analysis predicted the impact of variants on protein structure.
• Immunofluorescence microscopy visualized microtubule network alterations in transfected cells.

Main Results:

• A novel compound heterozygous mutation (p.Arg306Serfs*21 and p.His28Tyr) in TUBB8 was identified in infertile patients with early embryonic arrest.
• A benign variant (p.Thr429Met) did not impair fertility.
• The p.Arg306Serfs*21 mutation disrupted microtubule structure and led to truncated protein production.

Conclusions:

• The study expands the known spectrum of TUBB8 mutations associated with female infertility and early embryonic developmental arrest.
• These findings aid in genetic counseling for families with unexplained infertility.