Functional and clinical evidence for two novel heterozygous BUB1B variants and their value in precision genetic counseling for recurrent pregnancy loss - Report - MDSpire

Functional and clinical evidence for two novel heterozygous BUB1B variants and their value in precision genetic counseling for recurrent pregnancy loss

  • By

  • Tian-ying Wei

  • Ming-xian Kang

  • Ge-han Zhang

  • Jing Zhang

  • Jia-en Liu

  • Jing Ma

  • Ya-ping Tian

  • Hua-ying Hu

  • June 26, 2026

  • 0 min

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Clinical Report: Insights into Heterozygous BUB1B Variants in RPL

Overview

This study identifies two novel heterozygous BUB1B variants associated with recurrent pregnancy loss (RPL) and elevated rates of premature chromatid separation (PCS) in affected individuals.

Background

Recurrent pregnancy loss (RPL) affects a significant number of couples and often lacks a clear etiology. Chromosomal instability, particularly premature chromatid separation (PCS), has been implicated in RPL, with the BUB1B gene playing a role in maintaining spindle assembly checkpoint (SAC) function.

Data Highlights

VariantTypeEffect
c.2164T>CMissensep.W722R
c.2215G>TMissensep.A739S

Key Findings

  • Identification of two novel heterozygous BUB1B variants (c.2164T>C and c.2215G>T) in probands with unexplained RPL.
  • Both variants classified as variants of uncertain significance (VUS) according to ACMG/AMP guidelines.
  • Elevated PCS rates observed in lymphocytes of variant carriers compared to healthy controls.
  • Preliminary evidence of reduced BUB1B mRNA and BUBR1 protein expression in variant carriers.

Clinical Implications

The identification of BUB1B variants in RPL patients may warrant consideration for genetic screening in cases of unexplained pregnancy loss.

Conclusion

This study links heterozygous BUB1B variants to recurrent pregnancy loss.

Related Resources & Content

  1. Frontiers, 2026 -- Functional and clinical evidence for two novel heterozygous BUB1B variants and their value in precision genetic counseling for recurrent pregnancy loss
  2. The ASCO Post — Enhanced Surveillance and Risk-Reducing Intervention Options for Individuals With PALB2 Variants
  3. The Journal of Clinical Endocrinology & Metabolism — Effects of Rare Coding Variants in Severe Early-Onset Obesity Genes in the Population-Based UK Biobank Study
  4. Drug Safety — Discussion on "Leveraging Human Genetic Variants to Anticipate Drug Safety Concerns: Insights from PCSK9 Inhibitors
  5. Blood Cancer Journal — Analysis of uncommon germline mutations in familial cases of multiple myeloma
  6. Recurrent pregnancy loss: a committee opinion (2026) | American Society for Reproductive Medicine | ASRM
  7. Recurrent Pregnancy Loss
  8. Preimplantation genetic testing for aneuploidy in unexplained recurrent pregnancy loss: a systematic review and meta-analysis - ScienceDirect
  9. Frontiers | Functional and clinical evidence for two novel heterozygous BUB1B variants and their value in precision genetic counseling for recurrent pregnancy loss

Original Source(s)

Functional and clinical evidence for two novel heterozygous BUB1B variants and their value in precision genetic counseling for recurrent pregnancy loss

  • by Tian-ying Wei, Ming-xian Kang, Ge-han Zhang, Jing Zhang, Jia-en Liu, Jing Ma, Ya-ping Tian, Hua-ying Hu

  • June 26, 2026

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