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.

scholarly journals Compound Heterozygous Nonsense Mutations Leading to Hereditary Deficiency of Coagulation Factor XI in a Chinese Pedigree

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5032-5032
Author(s):  
Qian Li ◽  
Hui Zeng ◽  
Yong Xu ◽  
Min Zhou ◽  
Bing Chen ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Direct Sequencing ◽  
Gene Mutations ◽  
Coagulation Factor ◽  
Compound Heterozygous ◽  
Sequencing Analysis ◽  
Factor Xi ◽  
Nonsense Mutations ◽  
Prolonged Aptt ◽  
Dna Sequencing Analysis

Abstract The objective is to identify the gene mutations responsible for the deficiency of factor XI (FXI) in a Chinese pedigree. The FXI activity was tested with clotting assay. The F11 gene was amplified by PCR with direct sequencing. ClustalX-2.1-win and three online bioinformatics softwares were used to study the conservatism and harm of the mutation. The proband was a 70-year-old male and had a prolonged APTT of 67.8s. The corrected APTT was 28.3s and he had reduced FXI: activity of 0.8%. His son and daughter had normal APTT of 26s and 27.3s and FXI:C of 72% and 75%, respectively. DNA sequencing analysis showed the proband carried a compound heterozygous g.841C>T and g.1556G>A mutation , resulting in Ser281Stop and Trp519Stop, respectively, which caused premature termination of transcription in the F11. His son had the heterozygous g.841C>T mutation of F11 and his daughter had the heterozygous g.1556G>A mutation of F11. The three bioinformatics softwares indicated that the mutation had affected the function of the protein. The two nonsense mutations had been reported previously in different patient, but this is the first time to be reported in the proband, which was responsible for the decrease of FXI: activity. Disclosures No relevant conflicts of interest to declare.

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.

Asymptomatic Familial Factor XI Deficiency.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4449-4449
Author(s):  
Juan Herrada ◽  
Maria Chona Aloba ◽  
Dorothy M Adcock ◽  
Anuradha Gupta ◽  
Luis S. Noble ◽  
...  
Keyword(s):  
Reference Range ◽  
Conflicts Of Interest ◽  
Coagulation Factor ◽  
Normal Serum ◽  
Laboratory Evaluation ◽  
White Female ◽  
Factor Xii ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Family Medical History

Abstract Abstract 4449 Background Factor XI deficiency (known as Rosenthal syndrome or hemophilia C) is an autosomal disorder affecting both sexes which results in a bleeding disorder of variable severity. This condition is very uncommon among the non-Jewish population and consists mostly of sporadic cases, although an occasional familial cluster has been described (Bolton-Maggs et al. J Thromb Haemost 2004 Jun;2(6):918-24). We present two asymptomatic siblings with coagulation Factor XI deficiency. Case Report In February 2004 a healthy 33 year-old non-Jewish white female without personal or family medical history presented with an elevated partial thromboplastin time (PTT) incidentally found during a routine pre-operative evaluation. Her prothrombin time (PT) was normal. Her PTT was 45 seconds (reference interval 23-37 seconds), and normalized with 1:1 mixing studies of patient and normal plasma. Preliminary laboratory evaluation included negative tests for the presence of a Lupus Anticoagulant, a normal serum albumin level, and a normal urinalysis. Additional laboratory testing of coagulation and included FXI and XII activities, measured by means of a one stage APTT-based clotting assay using APTT reagent (Automated APTT, Trinity Biotech, Bray Ireland), congenitally depleted deficient plasma (HRF, Inc, Raleigh NC) using the MDA II Trinity Biotech, Bray Ireland). FXI was 46% (reference range 60-150) and FXII was 42% (reference range 50-150). In March 2004, a repeated the laboratory evaluation showed a FXI of 41% and a FXII of 46%. In April 2006, FXI was 49%, and FXII was 40%. Is to be noted that the patient never had abnormal bleeding episodes despite abdominal and breast surgical procedures. In 2009, her only brother (aged 29 and otherwise healthy) underwent hematological evaluation that showed normal levels of PT, PTT, platelet count, fibrinogen, and factor XII (88% activity). His factor XI was 51% (decreased activity). Conclusion Although modern laboratory methods are able to identify unusual coagulation defects, their clinical significance requires additional investigation. Disclosures: No relevant conflicts of interest to declare.

Genetic analysis of a pedigree with hereditary coagulation factor XI deficiency

2019 ◽  
Vol 30 (8) ◽  
pp. 413-418
Author(s):  
Xingxing Zhou ◽  
Haiyue Zhang ◽  
Mingshan Wang ◽  
Shasha Luo ◽  
Siqi Liu ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Coagulation Factor ◽  
Factor Xi ◽  
Factor Xi Deficiency

Molecular Genetic Analysis of Factor XI Deficiency: Identification of Five Novel Gene Alterations and the Origin of Type II Mutation in Portuguese Families

2000 ◽  
Vol 84 (11) ◽  
pp. 833-840 ◽  
Author(s):  
Célia Ventura ◽  
Ana I. Santos ◽  
Alice Tavares ◽  
Teresa Gago ◽  
João Lavinha ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Molecular Genetic ◽  
Coagulation Factor ◽  
Molecular Genetic Analysis ◽  
Null Alleles ◽  
Type Ii ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Premature Termination Codons ◽  
Gene Alterations

SummaryCoagulation factor XI (FXI) deficiency is an inherited autosomal recessive mild bleeding disorder. In this study, we report the molecular genetic analysis of FXI deficiency in six unrelated families of Portuguese origin. The Jewish type II mutation was found in two families, of seemingly Portuguese origin. Haplotype analysis in these families demonstrated that this mutation is of Jewish origin. In the remaining families, five novel FXI mutations have been identified. Two of these mutations (FXI IVS K -10T→A and FXI 1026G→T, cd 324) affect the FXI pre-mRNA splicing. A further two (FXI 307 ins AAGCAAT, cd 85 and FXI 1072 del A, cd 340) introduce frameshifts leading to premature termination codons. The FXI splicing mutation, 1026G→T cd 324, was found in compound heterozygosity with missense mutation FXI K518N. Analysis of the FXI mRNA from the latter genotype demonstrated new donor splice site usage. All reported mutations most likely result in functional null-alleles. In addition, three novel polymorphisms have been identified: at nt -138 in intron A, at codon D125 in exon 5 and at codon T249 in exon 8.

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 Diagnosis and Treatment of Acquired Hemophilia: One Single-Center Experience from PR. China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4250-4250
Author(s):  
Rong-Fu Zhou ◽  
Yueyi Xu ◽  
Wenjin Gao
Keyword(s):  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Coagulation Factor ◽  
Factor Vii ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Coagulation Factor Vii ◽  
Prolonged Aptt ◽  
Inhibitor Titer

Abstract Objective: To deepen the understanding of the clinical manifestations of acquired hemophilia A for timely and correctly treatment. Methods: The clinical data of the acquired hemophilia A patients diagnosed in the hospital from Jan 2006 to Mar 2021 were retrospectively analyzed, and the relevant literature was reviewed. Results: 17 patients with acquired hemophilia A, male: female =10: 7, median age 61 years (19 to 78 years), were diagnosed and treated in the hospital with the median time from the onset to diagnosis 21 days (2 days to 6 months). Six patients had comorbidity, including hepatitis B carrying, chronic myelomonocytic leukemia, diabetes, hypertension and positive autoantibodies, pemphigoid and gastric cancer, respectively. Other 11 patients were healthy before the onset. All patients had large large ecchymosis of skin, and one case was combined with hematuria, and one case with retroperitoneal hematoma. All patients had APTT extension (45s-144.7s) and the prolonged APTT could not be corrected with normal mixed plasma with and without incubation at 37℃ for 2 hours. FVIII activity was 1% - 8.9% and inhibitor titer 2 - 128 Bu/ml. All patients with bleeding were with prothrombin complex/recombinant activated coagulation factor VII, some of them with pd-coagulation factor FVIII preparations. Inhibitors were removed with prednisone acetate (1 case) + chemotherapy (1 case), prednisone acetate / + CTX (11 cases) + chemotherapy (1 case), prednisone acetate/prednisolone + mabthera (2 cases) + CTX (1 case), respectively. The removal time of inhibitor was from 8 days to 4 years. During the treatment process, two patients developed lower extremity venous thrombosis, and one patient was complicated with lung infection. Conclusion: Patients with unexplained bleeding and prolonged APTT should be conducted normal mixed plasma correction test, coagulation factor activity and inhibitor titer examination. After correctly diagnosis, bypass agents /coagulation factor VIII preparations should be given timely for hemostasis, protocol based on glucocorticoid + CTX/mabthera to remove the inhibitor and symptomatic treatment for patients with primary comorbidity disease at the same time. Disclosures No relevant conflicts of interest to declare.

CTSC compound heterozygous mutations in two Chinese patients with Papillon–Lefèvre syndrome

Oral Diseases ◽  
2019 ◽  
Vol 25 (5) ◽  
pp. 1394-1402 ◽  
Author(s):  
Yuelin Wu ◽  
Lei Zhao ◽  
Chunmei Xu ◽  
Yafei Wu
Keyword(s):  
Chinese Patients ◽  
Compound Heterozygous ◽  
Compound Heterozygous Mutations
Sign in / Sign up

Export Citation Format

Share Document