Expanded alleles of the FMR1 gene are related to unexplained recurrent miscarriages

Abstract

Up to 50% of recurrent miscarriage cases in women occur without an underlying etiology. In the current prospective case–control study, we determined the impact of CGG trinucleotide expansions of the fragile-X mental retardation 1 (FMR1) gene in 49 women with unexplained recurrent miscarriages. Case group consisted of women with two or more unexplained consecutive miscarriages. Blood samples were obtained and checked for the presence of expanded alleles of the FMR1 gene using PCR. Patients harboring the expanded allele, with a threshold set to 40 repeats, were further evaluated by sequencing. The number of abortions each woman had, was not associated with her respective CGG repeat number (P=0.255). The repeat sizes of CGG expansion in the FMR1 gene were significantly different in the two population groups (P=0.027). All the positive cases involved intermediate zone carriers. Hence, the CGG expanded allele of the FMR1 gene might be associated with unexplained multiple miscarriages; whether such an association is coincidental or causal can be confirmed by future studies using a larger patient cohort.

Curvilinear Association Between Language Disfluency and FMR1 CGG Repeat Size Across the Normal, Intermediate, and Premutation Range

“…This study highlights intermediate alleles as an opportunity for future research. Prior investigations of intermediate alleles have focused primarily on movement disorders and reproductive function (e.g., Bodega et al, 2005 ; Debrey et al, 2016 ; Entezari et al, 2017 ; Wang et al, 2017 ) and findings are controversial, as not all reports indicate increased risk in these areas ( Toft et al, 2005 ; Bennett et al, 2010 ; Kline et al, 2014 ). To our knowledge, no prior studies have investigated cognitive or linguistic phenotypes relative to intermediate alleles, which is a fruitful avenue of future investigation as intermediate alleles affect a significant proportion of the population (about 1:57 individuals; Cronister et al, 2008 ).…”

Preconception anti‐annexin A5 antibodies are associated with subsequent live birth in women with recurrent miscarriage: A retrospective study from China

“…The incidence of RM is estimated to be between 1% and 5%, threatening the fertility of women of childbearing age 2,3 . The causes of RM are multifaceted and may involve various factors such as endocrine imbalances, immune disorders, genetic predispositions, uterine anomalies, and blood clotting disorders 4–7 . There is mounting evidence that the presence of diseases and associated autoantibodies may increase the risk of miscarriage 8,9 .…”

“…2,3 The causes of RM are multifaceted and may involve various factors such as endocrine imbalances, immune disorders, genetic predispositions, uterine anomalies, and blood clotting disorders. [4][5][6][7] There is mounting evidence that the presence of diseases and associated autoantibodies may increase the risk of miscarriage. 8,9 Antiphospholipid antibodies (aPL) are a diverse group of autoantibodies linked to thrombotic events and miscarriage.…”

Effect of STOX1 on recurrent spontaneous abortion by regulating trophoblast cell proliferation and migration via the PI3K/AKT signaling pathway

“…[5][6][7][8] Recently, the dysfunction and dysregulated expression of correlative genes were reported to play a pivotal role in the risk of miscarriage. 9,10 A previous study demonstrated that unexplained RSA was probably associated with Foxp3 dysfunction and its abnormal expression, which could suppress the regulatory function of Treg cells and resulted in the failure of fetal-maternal immunologic tolerance. 11 In addition, the aberrant expression of ARNT-like protein 1 could regulate RSA through inhibiting trophoblast migration and invasion by the SP1-DNMT1/DAB2IP pathway.…”

“…A number of studies have shown that factors including cytogenetic abnormalities, anatomic irregularities, endocrine disorders, infection, autoimmunity, atypical blood clotting, sperm quality, and environmental factors can possibly induce miscarriage . Recently, the dysfunction and dysregulated expression of correlative genes were reported to play a pivotal role in the risk of miscarriage . A previous study demonstrated that unexplained RSA was probably associated with Foxp3 dysfunction and its abnormal expression, which could suppress the regulatory function of Treg cells and resulted in the failure of fetal‐maternal immunologic tolerance .…”