scholarly journals Embryonic lethal genetic variants and chromosomally normal pregnancy loss

2021 ◽  
Vol 116 (5) ◽  
pp. 1351-1358 ◽  
Author(s):  
Jennie Kline ◽  
Badri Vardarajan ◽  
Avinash Abhyankar ◽  
Sonja Kytömaa ◽  
Bruce Levin ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Pregnancy Loss ◽  
Normal Pregnancy ◽  
Embryonic Lethal

scholarly journals Embryonic lethal genetic variants and chromosomally normal pregnancy loss

2020 ◽  
Author(s):  
Jennie Kline ◽  
Badri N. Vardarajan ◽  
Avinash Avabhyankar ◽  
Sonja Kytömaa ◽  
Bruce Levin ◽  
...  
Keyword(s):  
Mental Health ◽  
Exome Sequencing ◽  
Genetic Variants ◽  
Pregnancy Loss ◽  
De Novo ◽  
Normal Pregnancy ◽  
National Database ◽  
Embryonic Lethal ◽  
Rare Genetic Variants ◽  
Lethal Genes

AbstractSTUDY QUESTIONAre rare genetic variants in the conceptus associated with chromosomally normal pregnancy loss?SUMMARY ANSWERThe proportion of probands with at least one rare variant is increased in chromosomally normal loss conceptuses compared with controls.WHAT IS ALREADY KNOWNAmong non-consanguineous families, one study of seven chromosomally normal losses to four couples with recurrent pregnancy loss (RPL) and a case report of a family with RPL of which one was known to be chromosomally normal identify compound heterozygote variants in three different genes as possibly causal. Among consanguineous families, RPL of chromosomally normal pregnancies with non-immune hydrops fetalis (NIHF) has been attributed to recessive variants in genes previously implicated for NIHF and new candidate genes.STUDY DESIGN, SIZE, DURATIONThe starting sample was 52 chromosomally normal losses to 50 women, identified in 2003-2005 as part of a cohort study on trisomy and ovarian aging. The analytic sample comprises 19 conceptus-parent trios with DNA from 17 biologic parents (cases). The control group derives from the National Institutes of Mental Health’s National Database for Autism Research (NDAR). It comprises 547 trios of unaffected siblings of autism cases and their parents.PARTICIPANTS/MATERIALS, SETTING, METHODSWe use exome sequencing to identify rare variants in the coding region of the genome. We defined variant rarity in two ways: ultra-rare (absent in gnomAD) and rare (heterozygote <10−3 in gnomAD). For autosomal recessives, we further required that the variant was absent as a homozygote in gnomAD. We compare the rates of rare predicted damaging variants (loss of function and missense – damaging) and the proportions of probands with at least one such variant in cases versus controls. Secondarily, 1) we repeat the analysis limiting it to variants in genes considered causal in fetal anomalies and 2) we compare the proportions of cases and controls with damaging variants in genes which we classified as possibly embryonic lethal based on a review which was blinded to case-control status.MAIN RESULTS AND THE ROLE OF CHANCEThe rates of ultra-rare damaging variants (all de novo) are 0.21 and 0.17 in case and control probands, respectively. The corresponding rates for rare potentially pathogenic de novo variants are 0.37 and 0.24, respectively; for autosomal recessive variants they 0.11 and 0.03. The proportions of probands with at least one rare potentially damaging variant were 36.8% among cases and 22.9% among controls (odds ratio (OR) = 2.0, 95% CI 0.9, 3.0). Secondary analyses show no damaging variants in fetal anomaly genes among case probands; the proportion with variants in possibly embryonic lethal genes was increased in case probands (OR=14.5, 95% CI 3.4, 61.1). Cases had variants in possibly embryonic lethal genes BAZ1A, FBN2 and TIMP2. Post hoc review of these cases suggests that CDH5 may also be an embryonic lethal gene.LIMITATIONS, REASONS FOR CAUTIONThe number of case trios (n=19) limits the precision of our point estimates. We observe a moderate association between rare damaging variants and chromosomally normal loss with a confidence interval that includes unity. A larger sample is needed to estimate the magnitude of the association with precision and to identify the relevant biological pathways.WIDER IMPLICATIONS OF THE FINDINGSOur data add to a very small literature on this topic. They suggest rare genetic variants in the conceptus may be a cause of chromosomally normal loss.TRIAL REGISTRATION NUMBERN/A.STUDY FUNDING/COMPETING INTERESTS(S)Exome sequencing of case trios was performed by Baylor-Hopkins Center for Mendelian Genomics through National Human Genome Research Institute grant 5U54HG006542.Data used in the preparation of this manuscript were obtained from the National Institute of Mental Health (NIMH) Data Archive (NDA). NDA is a collaborative informatics system created by the National Institutes of Health to provide a national resource to support and accelerate research in mental health. Dataset identifier(s): src_subject_id. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or of the Submitters submitting original data to NDA.No author has a competing interest.

The relationship between vitamin D receptor (VDR) rs2228570 and rs7975232 genetic variants and the risk of recurrent pregnancy loss

Meta Gene ◽  
2021 ◽  
Vol 27 ◽  
pp. 100833
Author(s):  
Zohreh Salari ◽  
Nasrollah Saleh-Gohari ◽  
Monire Rezapour ◽  
Ahamad Khosravi ◽  
Hadi Tavakkoli ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Genetic Variants ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
The Relationship

scholarly journals Prevalence of anticardiolipin antibody in Bangladeshi patients with recurrent pregnancy loss

1970 ◽  
Vol 36 (1) ◽  
pp. 10-13 ◽  
Author(s):  
A.S.M. Giasuddin ◽  
Ishrat Mazhar ◽  
A.M. Mujibul Haq
Keyword(s):  
Blood Group ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Anticardiolipin Antibody ◽  
Serum Levels ◽  
Normal Pregnancy ◽  
Control Serum

The objective of the present study was to see the prevalence of anticardiolipin antibody (ACA) in Bangladeshi patients (35) with recurrent pregnancy loss. Thirty-seven women with normal pregnancy were included as control. Serum levels (mean ± SD) of ACA (u/mL) was significantly higher, whereas ANA (Ab-index) and anti-dsDNA (Ab-index) were similar in cases compared to controls (Cases vs Controls g ACA: 31.8 ± 24.3 vs 10.5 ± 3.4, p<0.001; ANA: 1.07 ± 0.34 vs 0.92 ± 0.15, p>0.5; A-dsDNA: 0.53 ± 0.16 vs 0.52 ± 0.18, p>0.5). The cases positive for ACA, ANA and anti-dsDNA were 37.1% (p<0.001), 20% (p>0.05) and 2.8% (p>0.1) respectively. Among the seropositive cases 4/35 (11.4%) and 4/13 (30.8%) were positive for both ACA and ANA. In controls only 2/37 (5.4%) and 2/37 (5.4%) were positive for ACA and ANA respectively and none were positive for both ACA and ANA together simultaneously. Significantly high proportion of cases had O positive blood group (23/35: 65.7%, 10/13: 76.9%) (p<0.01). The prevalence of ACA varies according to population being 37.1% (13/35) in our patients with recurrent pregnancy loss and 5.4% in controls.Online: 13 July 2010DOI: http://dx.doi.org/10.3329/bmrcb.v36i1.5446Bangladesh Med Res Counc Bull 2010; 36: 10-13 

Anti-fibrillin-1 autoantibodies in normal pregnancy and recurrent pregnancy loss

2011 ◽  
Vol 10 (3) ◽  
pp. 131-136 ◽  
Author(s):  
Milena Atanasova Atanasova ◽  
Emiliana Ilieva Konova ◽  
Tania Ace Aleksovska ◽  
Katia Nikolova Todorova ◽  
Miglena Nikolaeva Georgieva ◽  
...  
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Normal Pregnancy ◽  
Fibrillin 1

scholarly journals Impaired Gal-9 Dysregulates the PBMC-Induced Th1/Th2 Imbalance in Abortion-Prone Matings

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mengzhou He ◽  
Ming Jiang ◽  
Yuan Zhou ◽  
Fanfan Li ◽  
Meitao Yang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Pregnancy Loss ◽  
Mononuclear Cells ◽  
Recurrent Miscarriage ◽  
Normal Pregnancy ◽  
Immune Deviation ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Th2 Immunity ◽  
Maternal Fetal Interface

Recurrent miscarriage is defined as the loss of 3 or more consecutive pregnancies; however, the underlying immunologic mechanisms that trigger pregnancy loss remain largely unelucidated. Galectin-9 (Gal-9) may modulate a variety of biologic functions and play an important role in Th1/Th2 immune deviation. To analyze the mechanism of Gal-9 in abortion, we used the classical abortion-prone mouse model (DBA/2-mated CBA/J mice) to detect the expression of Gal-9 at the maternal-fetal interface. We also mimicked the immune environment of pregnancy by culturing trophoblast cells with peripheral blood mononuclear cells (PBMCs) to explore how Gal-9 might be involved in the pathogenesis of abortion. We found that the expression levels of Gal-9 in abortion-prone matings were lower than that for controls. Using a coculture system, we detected a Th1 preponderance in the coculture from abortion-prone matings. Furthermore, Gal-9 blockade augmented the imbalance of Th1/Th2 immunity in abortion-prone matings by promoting the secretion of Th1-derived cytokines in coculture, while there was a Th2 preponderance when we administered recombinant Gal-9. In conclusion, our results suggest that the Gal-9 signal is important for the regulation of PBMC function toward a Th2 bias at the maternal-fetal interface, which is beneficial for the maintenance of a normal pregnancy.

scholarly journals Application of Embryonic Lethal or Other Obvious Phenotypes to Characterize the Clinical Significance of Genetic Variants Found in Trans with Known Deleterious Mutations

2005 ◽  
Vol 65 (21) ◽  
pp. 10096-10103 ◽  
Author(s):  
Thaddeus Judkins ◽  
Brant C. Hendrickson ◽  
Amie M. Deffenbaugh ◽  
Kristilyn Eliason ◽  
Benoît Leclair ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Genetic Variants ◽  
Deleterious Mutations ◽  
Embryonic Lethal ◽  
In Trans

scholarly journals Prevalence of Some Gene Polymorphisms Related to Early Pregnancy Loss among Russian Women

2019 ◽  
Vol 23 (4) ◽  
pp. 381-389
Author(s):  
A. A. M. Ahmed ◽  
A. A. Muradian ◽  
M. M. Azova
Keyword(s):  
Early Pregnancy ◽  
Gene Polymorphisms ◽  
Pregnancy Loss ◽  
Previous History ◽  
Normal Pregnancy ◽  
Early Pregnancy Loss ◽  
Specific Pcr ◽  
Genetic Predictors ◽  
History Of ◽  
Allele Specific

Background. A variety of biological processes regulated by differential gene expression are required to maintain a normal gestation and accordingly, the mutations and polymorphisms in such genes may cause miscellaneous biological disorders that eventually result in early pregnancy loss. Many studies reported that aberrant fetal DNA methylation as well as embryonic chromosome abnormalities may lead to impairment of fetal early growth and development. Therefore, we have aimed to genotype several gene polymorphisms might be involved in the above-mentioned biological disorders to screen their prevalence in Russian population. Materials and methods. 81 Russian women without previous history of normal pregnancy or early abortion were recruited into this population study to determine the genotype and allele frequencies through genotyping using RFLP-PCR method for DNMT3B rs2424913, DNMT3B rs1569686, DNMT3A rs7590760, DNMT1 rs2228611, DNMT1 rs8101626, DNMT3L rs2276248, and DNMT3L rs2070565, allele-specific PCR for SYCP3 T657C, and real-time PCR for MTHFR rs1801133, MTHFR rs1801131, MTR rs1805087, and MTRR rs1801394. Results. Minor homozygous genotypes and minor alleles of the polymorphisms DNMT3B rs2424913 (TT: 11.1%, T: 37.05%), DNMT1 rs2228611 (GG: 18.5%, G: 40.75%), and DNMT1 rs8101626 (GG: 16.0%, G: 40.1%) were quite prevalent in Russian women and as frequent as those of the well-studied polymorphisms: MTRR rs1801394 (GG: 27.2%, G: 50.65%), MTHFR rs1801131 (CC: 17.3%, C: 40.15%), and MTHFR rs1801133 (TT: 11.1%, T: 29.0%).The heterozygous genotype of SYCP3 T657C (CT: 12.3%, T: 6.15%) was also quite frequent. Conclusion. Based on our study and literature data, we suggest that DNMT3B rs2424913, DNMT1 rs2228611, DNMT1 rs8101626, and SYCP3 T657C polymorphisms along with the common folate cycle gene polymorphisms can be potential genetic predictors for early pregnancy loss in Russian women.

ORIGINAL ARTICLE: Anti-Elastin Antibodies and Elastin Turnover in Normal Pregnancy and Recurrent Pregnancy Loss

2009 ◽  
Vol 61 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Emiliana Konova ◽  
Tania Aleksovska ◽  
Milena Atanasova ◽  
Miglena Georgieva ◽  
Katia Todorova ◽  
...  
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Normal Pregnancy

Comparison of gene expression at the feto–maternal interface between normal and recurrent pregnancy loss patients

2002 ◽  
Vol 14 (4) ◽  
pp. 235 ◽  
Author(s):  
Kwang-Hyun Baek ◽  
Bum Chae Choi ◽  
Jin-Hie Lee ◽  
Hee-Kyung Choi ◽  
Sook-Hwan Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Expression Patterns ◽  
Subtractive Hybridization ◽  
Normal Pregnancy ◽  
Chorionic Villi ◽  
Expression Of Genes ◽  
Different Levels ◽  
In Pregnancy

—Normal pregnancy requires a series of immunological, metabolic, vascular and endocrine regulating processes. However, the specific genes and proteins involved in these processes are not well defined. Aberration of these processes may lead to problems in pregnancy. One of these problems may be recurrent pregnancy loss (RPL). Little information is available on the level of expression of genes that may play a role in normal pregnancy. Therefore, this study determined whether different levels of gene expression at the feto-maternal interface could be associated with factors for RPL. The expression patterns of genes isolated from subtractive hybridization analysis performed with chorionic villi from normal and abnormal pregnancies were investigated. Eight genes classified into groups, including immunosuppression-related, embryo attachment-related and angiogenesis-related, were isolated.

Sign in / Sign up

Export Citation Format

Share Document