TERB1 – Female Infertility

This summary details the association between TERB1 (HGNC:26675) and female infertility (MONDO:0021124). Two independent case reports have identified homozygous, protein‐truncating variants in TERB1 in unrelated women presenting with primary infertility (PMID:38277113). These findings provide initial clinical support for TERB1’s role, adding it to the list of meiosis‐related genes implicated in reproductive dysfunction.

The genetic evidence is derived from two probands carrying truncating mutations, with one case additionally demonstrating segregation through an affected sibling (PMID:38277113). Specifically, one of the reported variants is formatted as: c.626G>A (p.Trp209Ter), meeting established HGVS criteria. Both cases were identified via Whole Exome Sequencing followed by confirmatory Sanger sequencing, ensuring high confidence in variant interpretation.

The inheritance pattern observed in these cases is autosomal recessive, with the phenotypic presentations occurring in the homozygous state. In the reported family, an affected relative (the azoospermic brother) further supports the segregation of the variant with the infertility phenotype. This familial evidence, although limited in number, reinforces the gene‐disease relationship.

Functional assessments, albeit conducted primarily in the context of male infertility, also provide supportive insights. Computational analyses of TERB1 missense variants have demonstrated deleterious impacts on protein structure and function, consistent with a role in meiotic chromosome dynamics. While these in silico studies (PMID:35342767) enhance our understanding of TERB1’s biological importance, direct functional assays in female reproductive tissues remain pending.

Integrating both the genetic and computational evidence, the association between TERB1 and female infertility is supported by the identification of truncating variants in affected individuals and by data underscoring TERB1’s critical role during meiosis. Notwithstanding the limited number of probands, these findings offer a clinically useful marker for diagnostic decision‑making and may guide further research toward elucidating the molecular underpinnings of female infertility.

Key Take‑home: TERB1 should be considered in the genetic evaluation of female infertility, as even limited genetic evidence paired with supporting functional data underlines its potential clinical utility.

References

• Journal of assisted reproduction and genetics • 2024 • A report of two homozygous TERB1 protein-truncating variants in two unrelated women with primary infertility PMID:38277113
• BioMed research international • 2022 • Computational Analysis of the Potential Impact of MTC Complex Missenses SNPs Associated with Male Infertility PMID:35342767

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