Abstract
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 language | English (US) |
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Pages (from-to) | 1351-1358 |
Number of pages | 8 |
Journal | Fertility and sterility |
Volume | 116 |
Issue number | 5 |
DOIs | |
State | Published - Nov 2021 |
Keywords
- Chromosomally normal
- embryonic lethal
- epidemiology
- genetic variants
- pregnancy loss
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology