Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A

Morio Arai, Miyoko Higuchi, Stylianos E. Antonarakis, Haig Kazazian, John A. Phillips, Robert L. Janco, Leon W. Hoyer

Research output: Contribution to journalArticle

Abstract

The molecular defect responsible for moderate and severe hemophilia A has been identified for two unrelated patients with the CRM-positive form of this disorder (factor VIII activity of 0.02 and 0.05 U/mL with factor VIII antigen of 0.87 and 2.20 U/mL). In both cases, the immunopurified dysfunctional factor VIII protein is abnormal, in that the 80 Kd light chain is not cleaved by thrombin at arginine-1689. The basis for this failure was identified by polymerase chain reaction amplification of exon 14 of the variant factor VIII genes and direct sequencing of the amplified products. In both cases, a single base substitution (C to T) was identified that produces an arginine to cysteine substitution at amino acid residue 1689. These data identify the molecular defects of the two identical factor VIII variant proteins. The dysfunctional factor VIII has been designated "Factor VIII-East Hartford," the residence of the patient in whom the defect was first identified.

Original languageEnglish (US)
Pages (from-to)384-389
Number of pages6
JournalBlood
Volume75
Issue number2
StatePublished - Jan 15 1990
Externally publishedYes

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Factor VIII
Hemophilia A
Thrombin
Genes
Mutation
Defects
Arginine
Substitution reactions
Polymerase chain reaction
Amino Acid Substitution
Cysteine
Amplification
Exons
Proteins
Light
Antigens
Amino Acids
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Hematology

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Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A. / Arai, Morio; Higuchi, Miyoko; Antonarakis, Stylianos E.; Kazazian, Haig; Phillips, John A.; Janco, Robert L.; Hoyer, Leon W.

In: Blood, Vol. 75, No. 2, 15.01.1990, p. 384-389.

Research output: Contribution to journalArticle

Arai, Morio ; Higuchi, Miyoko ; Antonarakis, Stylianos E. ; Kazazian, Haig ; Phillips, John A. ; Janco, Robert L. ; Hoyer, Leon W. / Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A. In: Blood. 1990 ; Vol. 75, No. 2. pp. 384-389.
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AU - Hoyer, Leon W.

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