Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a predictor of recurrent miscarriage

Ogasawara, Mayumi; Aoki, Koji; Katano, Kinue; Ozaki, Yasuhiko; Suzumori, Kaoru

doi:10.1016/s0015-0282(01)01688-0

Cited by 67 publications

(56 citation statements)

References 20 publications

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“…25 Other studies have found anti-FXII antibodies may alter platelet-FXII binding and promote pregnancy loss in humans. 13,15 Interestingly, Inomo et al 13 found 76.5% of their recurrent pregnancy loss subjects had antibodies that recognized amino acids 1 to 30 in the heavy chain of FXII (a region where monoclonal antibody B7C9 binds).…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Cat Factor XII Gene and Identification of a Mutation Causing Factor XII Deficiency in a Domestic Shorthair Cat Colony

et al. 2014

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Coagulation factor XII (FXII) may be important in cardiovascular and inflammatory diseases. We have identified and characterized a naturally occurring mutation in the feline FXII gene that results in a mutant protein and enzymatic loss of activity. Feline intron/ exon gene structure and sequence were acquired by comparing DNA sequences obtained from a fragmented Felis catus genomic sequence and the National Center for Biotechnology Information's Cross Species Megablast of multiple species' FXII gene sequences. Fourteen exons ranging in size from 57 to 222 base pairs were confirmed spanning 8 Kb on chromosome A1. The 1828-base pair feline FXII messenger RNA (mRNA) sequence contains an open reading frame that encodes a protein of 609 amino acids with high homology to human FXII protein. Total RNA and mRNA purified from liver tissue of 4 wild-type/normal and 8 FXII-deficient cats confirmed the predicted mRNA sequence and identified one important single-nucleotide polymorphism (SNP). A single base deletion in exon 11 of the FXII coding gene in our colony of cats results in deficient FXII activity. Translation of the mRNA transcript shows a frame shift at L441 (C441fsX119) resulting in a nonsense mutation and a premature stop codon with a predicted 560-amino acid protein. The mutant FXII protein is truncated in the 3 0 proteolytic light chain region of the Cterminus, explaining its loss of enzymatic activity. This study is the first molecular characterization of the feline FXII gene and the first identification of an FXII mutation in the domestic cat, providing insights into the origin and nature of feline FXII deficiency.Keywords coagulation, technology, cat, domestic mammals, species, factor XII, FXII, Hageman factor, gene, mutation, mRNA Deficiency of factor XII (FXII or Hageman factor) was first described in 1955 in a human patient who lacked plasma coagulant activity. 31 In the intervening time, FXIIs from multiple species have been genetically characterized and various mutations have been reported in humans. Although FXII deficiency does not present as a bleeding tendency, recent evidence indicates FXII may be important in maintaining blood clot stability and pregnancy. 22,25,32 A feline FXII-deficient case was first described in 1977, 10 and later Kier et al 18 established a colony in the early 1980s to study FXII deficiency.Today, these offspring continue to provide information about the in vivo role of FXII and are the source of this study's molecular characterization of a mutation in the FXII gene with a similar autosomal recessive inheritance pattern and coagulation profile as seen in humans. Studies in human populations indicate that the prevalence of moderate to severe FXII deficiency is between 2% and 5% of a given white population.11 Similar to humans, the prevalence of FXII deficiency in domestic cats of the United States is 2%. 3Factor XII is primarily produced in the liver and circulates in the plasma as an inactive precursor enzyme or zymogen. 40The FXII protein is a 2-chain molecule consis...

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Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Cat Factor XII Gene and Identification of a Mutation Causing Factor XII Deficiency in a Domestic Shorthair Cat Colony

et al. 2014

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“…It has been suggested that RPL of otherwise unknown origin might be associated with reduced FXII activities. A study of 424 pregnancies indicated that abnormal FXII levels were significantly more prevalent in patients with a history of repeated miscarriage [63]. Yamada et al also found an increased, but low, prevalence of 2.9% for FXII deficiency in 241 RPL patients [64].…”

Section: Introductionmentioning

confidence: 99%

Recurrent pregnancy loss: the key potential mechanisms

Baek

Lee

Kim

2007

Trends in Molecular Medicine

142

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“…8 Ogasawara et al examined various thrombophilic markers and found that plasma levels of FXII, but not protein C, protein S, and antithrombin III, are a predictor of IRM. 7 A positive association between reduced FXII activity and recurrent abortions has been documented across ethnic barriers. Recently, Jones et al found both IgM and IgG antibodies to FXII in the plasma of women with antiphospholipid syndrome and IRM, pointing to an autoimmune basis of reduced FXII activity in these women.…”

Section: Discussionmentioning

confidence: 99%

“…Ogasawara et al found that a decrease of FXII plasma levels is an independent risk factor for recurrent miscarriage. 7 The authors hypothesised that FXII deficiency may induce microthrombi at the maternal -fetal interface and thus impair adequate fetal growth. Recently, the FXII C46T polymorphism has been investigated in a Japanese population of women with IRM and no association was ascertained.…”

Section: Introductionmentioning

confidence: 99%

The C46T polymorphism of the coagulation factor XII gene and idiopathic recurrent miscarriage

Walch

Riener

Tempfer

et al. 2005

BJOG

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Thrombophilia has been described to be involved in the pathogenesis of idiopathic recurrent miscarriage (IRM). We investigated the association between IRM and a C!T polymorphism at nucleotide 46 in the 5V-untranslated region of the coagulation factor XII (FXII) gene. Two hundred and twelve women with a history of IRM and 149 healthy controls were tested by a mutagenically separated polymerase chain reaction assay (MS PCR). Allele and genotype frequencies were not significantly different between the study and the control groups. Our data suggest that the FXII gene is not a candidate gene for this condition.

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Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a predictor of recurrent miscarriage

Cited by 67 publications

References 20 publications

Molecular Characterization of Cat Factor XII Gene and Identification of a Mutation Causing Factor XII Deficiency in a Domestic Shorthair Cat Colony

Molecular Characterization of Cat Factor XII Gene and Identification of a Mutation Causing Factor XII Deficiency in a Domestic Shorthair Cat Colony

Recurrent pregnancy loss: the key potential mechanisms

The C46T polymorphism of the coagulation factor XII gene and idiopathic recurrent miscarriage

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