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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 a C to A transition in exon 5 results in the substitution of Cys-128 by a nonsense codon (FXI-C128X). The missense mutation results in a substitution within the protease domain of FXI. Molecular modelling locates this residue in a structurally conserved region of the protease domain and the amino acid substitution may therefore interfere with either chain folding and subsequent secretion or the stability of the protein in plasma. We conclude that the mutations which we have identified are responsible for the inherited abnormality in these patients.
Y Imanaka, and
K Lal, and
T Nishimura, and
P H Bolton-Maggs, and
E G Tuddenham, and
J H McVey
September 2010,
Haemophilia : the official journal of the World Federation of Hemophilia,
Y Imanaka, and
K Lal, and
T Nishimura, and
P H Bolton-Maggs, and
E G Tuddenham, and
J H McVey
January 1999,
British journal of haematology,
Y Imanaka, and
K Lal, and
T Nishimura, and
P H Bolton-Maggs, and
E G Tuddenham, and
J H McVey
January 2006,
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis,
Y Imanaka, and
K Lal, and
T Nishimura, and
P H Bolton-Maggs, and
E G Tuddenham, and
J H McVey
October 2003,
American journal of hematology,
Y Imanaka, and
K Lal, and
T Nishimura, and
P H Bolton-Maggs, and
E G Tuddenham, and
J H McVey
March 2003,
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi,
Y Imanaka, and
K Lal, and
T Nishimura, and
P H Bolton-Maggs, and
E G Tuddenham, and
J H McVey
August 2003,
American journal of hematology,
Y Imanaka, and
K Lal, and
T Nishimura, and
P H Bolton-Maggs, and
E G Tuddenham, and
J H McVey
August 2020,
International journal of hematology,
Y Imanaka, and
K Lal, and
T Nishimura, and
P H Bolton-Maggs, and
E G Tuddenham, and
J H McVey
October 2007,
Haematologica,
Y Imanaka, and
K Lal, and
T Nishimura, and
P H Bolton-Maggs, and
E G Tuddenham, and
J H McVey
December 1999,
British journal of haematology,
Y Imanaka, and
K Lal, and
T Nishimura, and
P H Bolton-Maggs, and
E G Tuddenham, and
J H McVey
January 2023,
Acta haematologica,
