Embryonic lethal genetic variants and chromosomally normal pregnancy loss
Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved..
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.
| Errataetall: |
CommentIn: Fertil Steril. 2021 Nov;116(5):1359. - PMID 34602259 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:116 |
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| Enthalten in: |
Fertility and sterility - 116(2021), 5 vom: 21. Nov., Seite 1351-1358 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kline, Jennie [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.11.2021 Date Revised 07.12.2022 published: Print CommentIn: Fertil Steril. 2021 Nov;116(5):1359. - PMID 34602259 Citation Status MEDLINE |
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| doi: |
10.1016/j.fertnstert.2021.06.039 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Embryonic lethal genetic variants and chromosomally normal pregnancy loss |
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| 500 | |a Date Completed 29.11.2021 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a CommentIn: Fertil Steril. 2021 Nov;116(5):1359. - PMID 34602259 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a OBJECTIVE: To examine whether rare damaging genetic variants are associated with chromosomally normal pregnancy loss and estimate the magnitude of the association | ||
| 520 | |a DESIGN: Case-control | ||
| 520 | |a 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 | ||
| 520 | |a PATIENT(S): Cases comprised 19 chromosomally normal loss conceptus-parent trios. Controls comprised 547 unaffected siblings of autism case-parent trios | ||
| 520 | |a INTERVENTION(S): None | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
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