A case of factor XI deficiency caused by compound heterozygous F11 gene mutation

Haemophilia ◽  
2009 ◽  
Vol 15 (2) ◽  
pp. 603-606 ◽  
Author(s):  
JING WANG ◽  
XUEFENG WANG ◽  
JING DAI ◽  
QIULAN DING ◽  
QIHUA FU ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Compound Heterozygous ◽  
Factor Xi ◽  
Factor Xi Deficiency

scholarly journals A molecular genetic study of factor XI deficiency

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1942-1948
Author(s):  
JF Hancock ◽  
K Wieland ◽  
RE Pugh ◽  
U Martinowitz ◽  
S Schulman ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Severe Bleeding ◽  
Compound Heterozygous ◽  
Type I ◽  
Bleeding Tendency ◽  
Factor Xi ◽  
Molecular Genetic Study ◽  
Factor Xi Deficiency ◽  
Increased Risk ◽  
Plasma Factor

Factor XI deficiency is a rare bleeding diathesis found predominantly in Ashkenazi Jewish kindreds. A recent study of six Jewish patients identified three distinct mutations (Types I, II, and III) in the factor XI gene that were sufficient to fully define the genotypes of the patients. We have investigated 63 patients with factor XI deficiency and find overall allele frequencies of 44% for the type II mutation, 31% for the type III mutation, and 0% for the type I mutation. Therefore, 25% of the mutant factor XI alleles in our sample remain undefined. However, the distribution of mutant alleles is significantly different between Jewish and non-Jewish populations with hitherto undefined mutations accounting for 84% of the disease alleles in non-Jewish patients. Plasma factor XI:C levels were found to differ significantly between different homozygous and compound heterozygous genotypes and the inheritance of the II/III genotype was found to carry an increased risk of the most severe bleeding tendency.

Compound Heterozygosity for a Novel Mutation Combined with G Insertion in Exon 13 Causes Severe Factor XI Deficiency in Patients of Japanese Origin.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4087-4087
Author(s):  
Nobutsune Ishikawa ◽  
Shinichiro Yasunaga ◽  
Motoaki Ohtsubo ◽  
Yoshihiro Takihara ◽  
Takashi Sato ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Novel Mutation ◽  
Gene Mutations ◽  
Compound Heterozygous ◽  
Type I ◽  
Ashkenazi Jews ◽  
Factor Xi ◽  
Inherited Disorders ◽  
Factor Xi Deficiency ◽  
Prolonged Aptt

Abstract Factor XI (FXI) deficiency is a rare autosomal recessive coagulopathy. However, it is one of the most common inherited disorders among Ashkenazi Jews. FXI deficiency is characterized by undetectable levels of FXI antigen and coagulant activity. Patients with FXI deficiency usually suffered from mild to moderate bleeding manifestations. Up to now, more than 80 gene mutations responsible for FXI deficiency have been reported including three common mutations (Type I, II and III) in Ashkenazi Jews. However, it has been reported that significantly higher frequency of allelic heterogeneity has been observed in different ethnic groups. We have studied the molecular basis of this disease in a Japanese family. Two children with FXI deficiency who are siblings have frequent epistaxis. Blood coagulation tests showed severely prolonged aPTT with normal PT. FXI coagulant activities of both patients were less than 1% activity. Their father and mother had normal aPTT, but the activities of FXI in parents showed 45% and 52% activities, respectively. Prolonged aPTT restored to normal range by the addition of recombinant Factor VIIa (NovoSevenR) dose-dependently, indicating the possible efficacy for the replacement therapy in this disorder. FXI gene mutations were screened by a PCR. We identified a novel mutation, C to G transversion in exon 12 in the FXI gene. The C to G transversion in exon 12 results in a missense mutaion (Q433E). That leads to the disruption of catalytic domain structure of FXI molecule. Another mutation was found in G insertion in exon 13, which was previously reported in only one Japanese patient, causes the frameshift, resulting in substitution of last 105 amino acids (Tyr503-Val607) with 32 abnormal amino acid residues. This change also induces the destruction of the catalytic domain of FXI. Thus, the compound heterozygous novel mutations found in Japanese are not identical to those in Ashkenazi Jews, suggesting that this mutation may not be of the same ancestry.

Clinical and Biological Determinants of Bleeding Manifestation in Congenital Factor XI Deficiency; A Systematic Review

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1407-1407 ◽  
Author(s):  
Milana Drakulic ◽  
Chatree Chai-Adisaksopha ◽  
Alfonso Iorio
Keyword(s):  
Gene Mutation ◽  
Bleeding Tendency ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Risk Of Bleeding ◽  
History Of ◽  
Surgical Bleeding ◽  
Bleeding Manifestation ◽  
Baseline Factor ◽  
Congenital Factor

Abstract Background: Congenital factor XI (FXI) deficiency is a rare inherited bleeding disorder caused by mutation of the FXI gene. Clinical manifestation and bleeding severity of FXI deficiency are varied. To our best knowledge, there are no studies investigating the predictors of bleeding in these patient population. Our study aims to investigate the clinical presentation of congenital FXI deficiency and to identify clinical, biological, and genetic determinants of bleeding. Methods: We conducted a systematic search in MEDLINE and EMBASE databases from inception to March 2016. We included the studies of congenital FXI deficiency. In terms of study design, we included prospective or retrospective studies as well as case series and case reports. We collected clinical characteristics of the patients including age, sex, family history of FXI deficiency, family history of bleeding, and site of bleeding. We also collected the laboratories including baseline aPTT, FXI level, and genetic test results. Results: There were 141 studies included in this review, involving 728 patients with reported congenital FXI deficiency. Forty-three percent of the patients were male. Clinical characteristics of the patients was demonstrated in Table 1. Of these, 421 (51.84%) patients had bleeding tendency. Surgical bleeding was the most common bleeding manifestation (31.88%), following bymucocutaneous bleeding (13.35%) and hypermenorrhea (9.11%). Factor XI gene mutation was found in 422 patients (57.97%). Type II mutation was the most common reported mutation (45.19%). With regards tozygosity of patients with gene mutation, 43.94% of patients had heterozygosity of factor XI gene mutation. Univariate analysis revealed that patients with baseline factor XI level less than 25% were associated with higher risk of bleeding (odd ratio 1.48 (95% confidence interval [CI]; 1.05 to 2.09). In addition, patients with combined mutation were at higher risk of bleeding when compared to patients with single mutation (odd ratio 2.83 (95% CI; 1.09-7.39). Conclusion: Our study found that patients with factor XI deficiency has mild bleeding manifestation. Half of the patients do not experience bleeding tendency. Surgical bleeding is the most common presentation in these patient population and likely to be the first bleeding symptom. Baseline factor XI level less than 25% is the predictor of bleeders as well as combined gene mutation. Table 1 Characteristics of patients with congenital factor XI deficiency Table 1. Characteristics of patients with congenital factor XI deficiency Disclosures No relevant conflicts of interest to declare.

A molecular genetic study of factor XI deficiency

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1942-1948 ◽  
Author(s):  
JF Hancock ◽  
K Wieland ◽  
RE Pugh ◽  
U Martinowitz ◽  
S Schulman ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Severe Bleeding ◽  
Compound Heterozygous ◽  
Type I ◽  
Bleeding Tendency ◽  
Factor Xi ◽  
Molecular Genetic Study ◽  
Factor Xi Deficiency ◽  
Increased Risk ◽  
Plasma Factor

Abstract Factor XI deficiency is a rare bleeding diathesis found predominantly in Ashkenazi Jewish kindreds. A recent study of six Jewish patients identified three distinct mutations (Types I, II, and III) in the factor XI gene that were sufficient to fully define the genotypes of the patients. We have investigated 63 patients with factor XI deficiency and find overall allele frequencies of 44% for the type II mutation, 31% for the type III mutation, and 0% for the type I mutation. Therefore, 25% of the mutant factor XI alleles in our sample remain undefined. However, the distribution of mutant alleles is significantly different between Jewish and non-Jewish populations with hitherto undefined mutations accounting for 84% of the disease alleles in non-Jewish patients. Plasma factor XI:C levels were found to differ significantly between different homozygous and compound heterozygous genotypes and the inheritance of the II/III genotype was found to carry an increased risk of the most severe bleeding tendency.

A novel factor XI gene mutation associated with mild factor XI deficiency in a symptomatic patient

2006 ◽  
Vol 17 (6) ◽  
pp. 499-502 ◽  
Author(s):  
Khaled M Ramadan ◽  
Orla McNulty ◽  
Julia AM Anderson ◽  
Francis G Jones ◽  
Paul C Winter
Keyword(s):  
Gene Mutation ◽  
Symptomatic Patient ◽  
Factor Xi ◽  
Factor Xi Deficiency

scholarly journals The Molecular Genetic Analysis of Coagulation Factor XI (FXI) Deficiency in Two Chinese Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5033-5033
Author(s):  
Rong-Fu Zhou ◽  
Qian Li ◽  
Min Zhou
Keyword(s):  
Genetic Analysis ◽  
Conflicts Of Interest ◽  
Coagulation Factor ◽  
Chinese Patients ◽  
Compound Heterozygous ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Software Analysis ◽  
Prolonged Aptt ◽  
Compound Heterozygous Mutations

Abstract Objective: To investigate the molecular pathogenesis of two coagulation factor XI (FXI) deficiency patients. Methods: The diagnosis was validated by coagulant assays: APTT and correct test, PT, INR and coagulation factors activities. Coagulation factor activity were tested with clotting assay. The patients' DNA were extracted and all exons and flanking sequences of FXI gene were amplified using PCR. After purified, the products were sent for sequencing directly, the mutations were detected by comparing with wild sequences and analyzed using some bioinformatics software. Results: The two patients were diagnosed as coagulation factor XI deficiency due to prolonged APTT and low activities of coagulation factor FXI. The results of APTT, FXI:C was 88.1s, 1.1% and 107.1s, 3.8% , respectively. Genetic analysis found that compound heterozygous mutations g.1251-1G > A and g.1271delT in the first patient and the sequencing results of TA plasmid clones showed that the two mutations were located on different single strands of chromosomes. Double heterozygous mutations g.1070A >G and g.1446C > G were detected in the second patient, resulting in Lys357Arg and Cys482Stop. Software analysis indicated the mutations probably brought amino acid sequence changed, protein features affected and splice site changed. Conclusion: Compound heterozygous mutations g.1251-1G > A, g.1271delT and g.1070A > G , g.1446C > G had been identified in two coagulation factor XI deficiency patients, which might be the cause of their prolonged APTT and low FXI:C. To the best of our knowledge, the four mutations are reported for the first time in the literature. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Acquired Factor XI Inhibitors in Two Patients with Hereditary Factor XI Deficiency

1984 ◽  
Vol 51 (03) ◽  
pp. 371-375 ◽  
Author(s):  
Kangathevy Morgan ◽  
Sandra Schiffman ◽  
Donald Feinstein
Keyword(s):  
Protein A ◽  
Lambda Light Chain ◽  
Factor Xi ◽  
Spontaneous Bleeding ◽  
Factor Xi Deficiency ◽  
Hereditary Factor ◽  
Coagulation Mechanism ◽  
Factor Xia ◽  
Polyclonal Igg ◽  
Glass Surfaces

SummaryTwo patients with hereditary factor XI deficiency developed inhibitors following plasma transfusions. Neither had severe spontaneous bleeding. The patients’ plasmas neutralized both factor XI in plasma, purified factor XI, and purified factor XIa. The inhibitor in both patients’ plasmas adsorbed to Protein A- Sepharose. The inhibitors eluted from Protein A-Sepharose were partially neutralized by kappa and lambda light chain antisera indicating that they were polyclonal IgG antibodies. Both inhibitors markedly decreased adsorption of factor XI to glass surfaces. The cleavage of factor XI by trypsin was unaffected by the inhibitors. The lack of severe spontaneous bleeding in both of these patients strongly suggests that an alternate coagulation mechanism bypassing factor XI must compensate for this severe defect.

Molecular analysis in 12 factor XI deficiency patients from China: Identification of three novel splicing mutations

2020 ◽  
Vol 192 ◽  
pp. 100-102
Author(s):  
Donglei Zhang ◽  
Xian Zhang ◽  
Boyang Sun ◽  
Huiyuan Li ◽  
Feng Xue ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Splicing Mutations
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