Embryonic lethal genetic variants and chromosomally normal pregnancy loss

Jennie Kline, Badri Vardarajan, Avinash Abhyankar, Sonja Kytömaa, Bruce Levin, Nara Sobreira, Andrew Tang, Amanda Thomas-Wilson, Ruiwei Zhang, Vaidehi Jobanputra

Research output: Contribution to journalArticlepeer-review


Objective: To examine whether rare damaging genetic variants are associated with chromosomally normal pregnancy loss and estimate the magnitude of the association. Design: Case–control. Setting: Cases were derived from a consecutive series of karyotyped losses at one New Jersey hospital. Controls were derived from the National Database for Autism Research. Patient(s): Cases comprised 19 chromosomally normal loss conceptus–parent trios. Controls comprised 547 unaffected siblings of autism case–parent trios. Intervention(s): None. Main Outcome Measure(s): The rate of damaging variants in the exome (loss of function and missense–damaging) and the proportions of probands with at least one such variant among cases vs. controls. Results: The proportions of probands with at least one rare damaging variant were 36.8% among cases and 22.9% among controls (odds ratio, 2.0; 99% confidence interval, 0.5–7.3). No case had a variant in a known fetal anomaly gene. The proportion with variants in possibly embryonic lethal genes increased in case probands (odds ratio, 14.5; 99% confidence interval, 1.5–89.7); variants occurred in BAZ1A, FBN2, and TIMP2. Conclusion(s): Rare genetic variants in the conceptus may be a cause of chromosomally normal pregnancy loss. A larger sample is needed to estimate the magnitude of the association with precision and identify relevant biologic pathways.

Original languageEnglish (US)
Pages (from-to)1351-1358
Number of pages8
JournalFertility and sterility
Issue number5
StatePublished - Nov 2021


  • Chromosomally normal
  • embryonic lethal
  • epidemiology
  • genetic variants
  • pregnancy loss

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology


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