Functional and clinical evidence for two novel heterozygous BUB1B variants and their value in precision genetic counseling for recurrent pregnancy loss - Scorecard - 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 Scorecard: Clinical and Functional Insights into Two New Heterozygous BUB1B Variants and Their Implications for Precision Genetic Counseling in Recurrent Pregnancy Loss

At a Glance

CategoryDetail
ConditionRecurrent Pregnancy Loss (RPL)
Key MechanismsPremature chromatid separation (PCS) linked to spindle assembly checkpoint (SAC) dysfunction.
Target PopulationIndividuals with unexplained recurrent pregnancy loss.
Care SettingGenetic counseling and reproductive health assessment.

Key Highlights

  • Identification of two novel heterozygous BUB1B variants (c.2164T>C and c.2215G>T).
  • Significantly elevated PCS rates in probands' lymphocytes compared to healthy controls.
  • Variants classified as variants of uncertain significance (VUS) per ACMG/AMP guidelines.
  • Preliminary evidence suggests a haploinsufficiency mechanism affecting SAC fidelity.
  • BUB1B screening recommended for RPL patients exhibiting PCS.

Guideline-Based Recommendations

Diagnosis

  • Genetic evaluation recommended in recurrent pregnancy loss cases.

Management

  • Consider BUB1B genetic screening in idiopathic RPL patients.

Monitoring & Follow-up

  • Monitor for PCS in peripheral blood lymphocytes of variant carriers.

Risks

  • Increased risk for reproductive challenges, including infertility and RPL.

Patient & Prescribing Data

Two unrelated families with recurrent pregnancy loss.

Insights into genetic counseling and potential assisted reproductive interventions.

Clinical Best Practices

  • Integrate genetic testing for BUB1B in RPL assessments.
  • Utilize multiple genetic analysis approaches including NGS and CMA.

Related Resources & Content

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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