The Progress of Research on Genetic Factors of Recurrent Pregnancy Loss

Li, Qinlan; Chen, Shuting; Dong, Xinyi; Fu, Shuai; Zhang, Tianyu; Wang, Zheng; Tian, Yonghong; Huang, Donghui

doi:10.1155/2023/9164374

Cited by 5 publications

(6 citation statements)

References 118 publications

(141 reference statements)

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“…The clinical symptoms of 3 and 5 were similar, polycystic kidney dysplasia and severe oligohydramnios. She only gave birth to one healthy daughter ( 2). The samples from the previous three abnormal pregnancies were not retained.…”

Section: Clinical Coursementioning

confidence: 99%

“…( 1), and c.2314del (p.M772*) was heterozygous in the proband ( 5) and mother ( 2). c.1415T>G (p.V472G) was not detected in mother and c.2314del (p.M772*) was not detected in father.…”

Section: Consent For Publicationmentioning

confidence: 99%

“…Recurrent pregnancy loss (RPL) is a devastating reproductive health burden, affects about 3-5% of couples trying to conceive globally (1). The etiology of RPL is complex, involving genetic abnormalities, metabolic disorders, autoimmune diseases, and endometrial dysfunction (2,3). The causes reason of RPL are still unknown in more than 50% of these couples.…”

Section: Introductionmentioning

confidence: 99%

“…The causes reason of RPL are still unknown in more than 50% of these couples. With the development of detection technology, genetic factors were found may play an essential role in unexplained RPL, such as chromosome abnormalities, copy number variants, single-gene changes and others (2). Previous researches reveal that the incidence of chromosome abnormalities in sporadic pregnancy loss was signi cantly higher than RPL (4).…”

Section: Introductionmentioning

confidence: 99%

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Two novel TMEM67 variations in a Chinese family with recurrent pregnancy loss: a case report

Pang,

Kong,

Tang

et al. 2024

Preprint

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Background:Recurrent pregnancy loss (RPL) is a common pregnancy complication that brings great pain to pregnant women and their families. Genetic factors are an important cause reason of RPL. However, clinical research on monogenic diseases with recurrent miscarriage is insufficient. Case presentation: Here we reported a Chinese family with RPL and genetic analysis of the abortion and parents. A paternally inherited heterozygous missense variant c.1415T>G (p.V472G) and a maternally inherited heterozygous nonsense variant c.2314del (p.M772*) in TMEM67gene were identified by trio-exome sequencing. c.2314del (p.M772*) generated a premature stop codon and truncated protein, was classified as “pathogenic”. c.1415T>G (p.V472G) located in extra-cellular region, was classified as “likely pathogenic”. Biallelic variants in TMEM67 gene cause lethal Meckel syndrome 3, consistent with the proband’s prenatal phenotype. Conclusion: The current study of the Chinese family expands the pathogenic variant spectrum of TMEM67and emphasizes the necessity of exome sequencing in RPL condition.

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Section: Clinical Coursementioning

confidence: 99%

“…( 1), and c.2314del (p.M772*) was heterozygous in the proband ( 5) and mother ( 2). c.1415T>G (p.V472G) was not detected in mother and c.2314del (p.M772*) was not detected in father.…”

Section: Consent For Publicationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Two novel TMEM67 variations in a Chinese family with recurrent pregnancy loss: a case report

Pang,

Kong,

Tang

et al. 2024

Preprint

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show abstract

“…Recurrent pregnancy loss (RPL) is a devastating reproductive health burden, affects about 3–5% of couples trying to conceive globally [ 1 ]. The etiology of RPL is complex, involving genetic abnormalities, metabolic disorders, autoimmune diseases, and endometrial dysfunction [ 2 , 3 ]. The causes reason of RPL are still unknown in more than 50% of these couples.…”

Section: Introductionmentioning

confidence: 99%

Two novel TMEM67 variations in a Chinese family with recurrent pregnancy loss: a case report

Pang,

Kong,

Tang

et al. 2024

BMC Med Genomics

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Background Recurrent pregnancy loss (RPL) is a common pregnancy complication that brings great pain to pregnant women and their families. Genetic factors are an important cause reason of RPL. However, clinical research on monogenic diseases with recurrent miscarriage is insufficient. Case presentation Here we reported a Chinese family with RPL and genetic analysis of the abortion and parents. A paternally inherited heterozygous missense variant c.1415T > G (p.V472G) and a maternally inherited heterozygous nonsense variant c.2314del (p.M772*) in TMEM67 gene were identified by trio-exome sequencing. c.2314del (p.M772*) generated a premature stop codon and truncated protein, was classified as “pathogenic”. c.1415T > G (p.V472G) located in extra-cellular region, was classified as “likely pathogenic”. Biallelic variants in TMEM67 gene cause lethal Meckel syndrome 3, consistent with the proband’s prenatal phenotype. Conclusion The current study of the Chinese family expands the pathogenic variant spectrum of TMEM67 and emphasizes the necessity of exome sequencing in RPL condition.

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Epigenetic role of LINE-1 methylation and key genes in pregnancy maintenance

Tisato,

Silva,

Scarpellini

et al. 2024

Sci Rep

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Spontaneous abortion is a pregnancy complication characterized by complex and multifactorial etiology. About 5% of childbearing women are globally affected by early pregnancy loss (EPL) and most of them experience recurrence (RPL). Epigenetic mechanisms and controlled inflammation are crucial for pregnancy maintenance and genetic predispositions may increase the risk affecting the maternal–fetal crosstalk. Combined analyses of global methylation, inflammation and inherited predispositions may contribute to define pregnancy loss etiopathogenesis. LINE-1 epigenetic regulation plays crucial roles during embryo implantation, and its hypomethylation has been associated with senescence and several complex diseases. By analysing a group of 230 women who have gone through pregnancy interruption and comparing those experiencing spontaneous EPL (n = 123; RPL, 54.5%) with a group of normal pregnant who underwent to voluntary interruption (VPI, n = 107), the single statistical analysis revealed significant lower (P < 0.00001) LINE-1 methylation and higher (P < 0.0001) mean cytokine levels (CKs: IL6, IL10, IL17A, IL23) in EPL. Genotyping of the following SNPs accounted for different EPL/RPL risk odds ratio: F13A1 rs5985 (OR = 0.24; 0.06–0.90); F13B rs6003 (OR = 0.23; 0.047–1.1); FGA rs6050 (OR = 0.58; 0.33–1.0); CRP rs2808635/rs876538 (OR = 0.15; 0.014–0.81); ABO rs657152 (OR = 0.48; 0.22–1.08); TP53 rs1042522 (OR = 0.54; 0.32–0.92); MTHFR rs1801133/rs1801131 (OR = 2.03; 1.2–3.47) and FGB rs1800790 (OR = 1.97; 1.01–3.87), although Bonferroni correction did not reach significant outputs. Principal Component Analysis (PCA) and logistic regression disclosed further SNPs positive/negative associations (e.g. APOE rs7412/rs429358; FGB rs1800790; CFH rs1061170) differently arranged and sorted in four significant PCs: PC1 (F13A, methylation, CKs); PC3 (CRP, MTHFR, age, methylation); PC4 (F13B, FGA, FGB, APOE, TP53, age, methylation); PC6 (F13A, CFH, ABO, MTHFR, TP53, age), yielding further statistical power to the association models. In detail, positive EPL risk association was with PC1 (OR = 1.81; 1.33–2.45; P < 0.0001) and negative associations with PC3 (OR = 0.489; 0.37–0.66; P < 0.0001); PC4 (OR = 0.72; 0.55–0.94; P = 0.018) and PC6 (OR = 0.61; 0.46–0.81; P = 0.001). Moreover, significant inverse associations were detected between methylation and CKs levels in the whole group (rIL10 = − 0.22; rIL17A = − 0.25; rIL23 = − 0.19; rIL6 = − 0.22), and methylation with age in the whole group, EPL and RPL subgroups (r2TOT = 0.147; r2EPL = 0.136; r2RPL = 0.248), while VPI controls lost significance (r2VPI = 0.011). This study provides a valuable multilayer approach for investigating epigenetic abnormalities in pregnancy loss suggesting genetic-driven dysregulations and anomalous epigenetic mechanisms potentially mediated by LINE-1 hypomethylation. Women with unexplained EPL might benefit of such investigations, providing new insights for predicting the pregnancy outcome and for treating at risk women with novel targeted epidrugs.

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The Progress of Research on Genetic Factors of Recurrent Pregnancy Loss

Cited by 5 publications

References 118 publications

Two novel TMEM67 variations in a Chinese family with recurrent pregnancy loss: a case report

Two novel TMEM67 variations in a Chinese family with recurrent pregnancy loss: a case report

Two novel TMEM67 variations in a Chinese family with recurrent pregnancy loss: a case report

Epigenetic role of LINE-1 methylation and key genes in pregnancy maintenance

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