Identification of two novel mutations in non‐Jewish factor XI deficiency

  title={Identification of two novel mutations in non‐Jewish factor XI deficiency},
  author={Yasufumi Imanaka and Kalpana Lal and Takuya Nishimura and Paula H B Bolton-Maggs and EDWARD G. D. Titddenham and John H. McVey},
  journal={British Journal of Haematology},
Summary. We have studied two heterozygous unrelated CRM non‐Jewish FXI‐deficient patients. Neither of the patients carries a previously described mutation. Their FXI genes were screened by SSCP analysis following PCR amplification of each exon and the flanking intronic sequences. DNA fragments showing aberrant mobility were cloned and sequenced. The following mutations were identified: in case 1, a T to G transition in exon 12 results in the substitution of Phe‐442 by Val (FXI‐F442V); in case 2… 
Identification of a novel mutation in a non‐Jewish factor XI deficient kindred
A large kindred of an Italian FXI‐deficient patient with a previously undescribed mutation is studied and it is concluded that this novel mutation occurred in a structurally conserved region and may therefore have interfered with either chain folding and secretion or stability of FXI and was responsible for the inherited abnormality seen in this kindred.
A novel mutation that leads to a congenital factor XI deficiency in a Japanese family
A novel mutation leading to a congenital deficiency of the coagulation factor XI (FXI) in a Japanese family is identified in exon 8 of the FXI gene and this patient inherited mutant alleles from her parents and is homozygous at this nucleotide position.
Characterization of seven novel mutations causing factor XI deficiency
Five FXI missense mutations (four novel) were associated with impaired secretion albeit normal dimerization, underscoring the existence of other mechanisms for defective secretion.
Identification of mutations and polymorphisms in the factor XI genes of an African American family by dideoxyfingerprinting.
Factor XI circulates as a homodimer, and the presence of mutations in both alleles of the factor XI gene suggests that his bleeding disorder is caused in part by the effect of the two abnormal gene products forming dimers in different combinations.
A common ancestral mutation (C128X) occurring in 11 non‐Jewish families from the UK with factor XI deficiency
Haplotype analysis of 11 families, including a further kindred previously reported from the USA, but which originally came from the UK (in which the index patient was homozygous for C128X), suggests a founder effect.
Molecular genetic analysis of severe coagulation factor XI deficiency in six Italian patients.
The identification and characterization of two novel mutations widen the mutational spectrum of FXI deficiency and reveal that patients carrying the type II mutation share a common haplotype, perhaps derived from a Jewish ancestor.
Molecular basis of severe factor XI deficiency in seven families from the west of France. Seven novel mutations, including an ancient Q88X mutation
A new ancient mutation in exon 4 resulting in Q88X, specific to patients from Nantes, that can result in a severely truncated polypeptide is identified, which is commonly found in individuals of Ashkenazi Jewish ancestry.
Factor XI deficiency in French Basques is caused predominantly by an ancestral Cys38Arg mutation in the factor XI gene.
Haplotype analysis based on the study of 10 intragenic polymorphisms was consistent with a common ancestry (a founder effect) for the Cys38Arg mutation, and Expression studies showed that Cys 38Arg and Cys237Tyr factor XI were produced in transfected baby hamster kidney cells, but their secretion was impaired.
A factor XI deficiency associated with a nonsense mutation (Trp501stop) in the catalytic domain
A novel mutation in an asymptomatic 65‐year‐old Japanese man with severe factor XI deficiency is identified, resulting in a substitution of Trp501 (TGG) by a stop codon (TAG) in the catalytic domain.
A factor XI deficiency associated with a nonsense mutation (Trp501stop) in the catalytic domain.
A novel mutation in an asymptomatic 65-year-old Japanese man with severe factor XI deficiency is identified, resulting in a substitution of Trp501 (TGG) by a stop codon (TAG) in the catalytic domain of exon 13, which abolished a FokI restriction site.


A molecular genetic study of factor XI deficiency.
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.
New amber mutation in a beta-thalassemic gene with nonmeasurable levels of mutant messenger RNA in vivo.
A beta-thalassemia gene that carries a novel nonsense mutation in a Chinese patient is identified and study of the expression of this cloned gene in a transient expression system demonstrated a 65% decrease in levels of normally spliced mutant beta-globin mRNA.
Factor XI deficiency in Ashkenazi Jews in Israel.
Type II and Type III mutations are the predominant causes of factor XI deficiency among Ashkenazi Jews, and genotypic analysis, assay for factor XI, and consideration of the type and location of surgery can be helpful in planning operations in patients with this disorder.
Nonsense mutation causing steroid 21-hydroxylase deficiency.
This mutation was carried by 3 of 20 unrelated patients with 21-hydroxylase deficiency alleles as determined by hybridization with a specific oligonucleotide probe, so that its presence in the abnormal CYP21B gene may be the result of a gene conversion event.
Haemophilia B: database of point mutations and short additions and deletions.
The seventh edition of the haemophilia B database lists in easily accessible form all known factor IX mutations due to small changes (base substitutions and short additions and/or deletions of <30
Nonsense mutations in the human beta-globin gene affect mRNA metabolism.
  • S. Baserga, E. Benz
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1988
The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation, and the effect depends on the location or the type of mutation.
High gene frequency of factor XI (PTA) deficiency in Ashkenazi Jews.
Factor XI deficiency can be added to the list of genetic disorders common to Ashkenazi Jews and patients with factor XI deficiency may bleed excessively following trauma, it is advisable to carry out the appropriate tests in anyAshkenazi Jewish patient undergoing surgery.
Organization of the gene for human factor XI.
Four independent recombinant lambda phage carrying overlapping DNA inserts that coded for the entire gene for factor XI were isolated and characterized by restriction mapping, Southern blotting, and selective DNA sequencing to establish the number and location of the intron-exon boundaries.
Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations.
Three independent point mutations that result in a blood coagulation abnormality have been identified in the factor XI gene of six unrelated Ashkenazi patients and no correlation was found between the three genotypes and the bleeding tendency in these patients.
Consequences of frameshift mutations at the immunoglobulin heavy chain locus of the mouse.
From an IgM secreting hybridoma line, 16 spontaneous mutants that produce truncated IgM polypeptides are isolated that express 3‐ to 100‐fold less mu‐mRNA and mutant mu‐protein than the parental cell line.