Three distinct point mutations in the factor IX gene of three Japanese CRM+ hemophilia B patients (factor IX B(M)Nagoya 2, factor IX Nagoya 3 and 4)

M. Hamaguchi, T. Matsushita, M. Tanimoto, I. Takahashi, K. Yamamoto, I. Sugiura, J. Takamatsu, K. Ogata, T. Kamiya, H. Saito

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Enzymatic DNA amplification and complete sequence analysis were used to investigate human factor IX coding sequences in three CRM+ hemophilia B patients. In a patient with severe hemophilia B and a markedly prolonged ox-brain prothrombin time, a C to T transition in exon VI changed the codon for Arg180 to Trp (factor IX B(M)Nagoya 2). This mutation would impair the cleavage by factor XIa required for activation of the zymogen. In a patient with mild hemophilia B, a G to A transition in exon VI changed the codon for Arg145 to His (factor IX Nagoya 3). This substitution also would be predicted to preclude the cleavage of factor IX by factor XIa at this peptide bond (Arg145-Ala146). Furthermore, this point mutation creates a new NlaIII restriction site which provides a quick and reliable method for carrier detection in the affected family members. A patient with severe hemophilia B (factor IX Nagoya 4) had a G to A transition in exon II changing the codon for Glu21 to Lys. This novel point mutation is assumed to impair the function of factor IX by disrupting the calcium binding of factor IX.

Original languageEnglish
Pages (from-to)514-520
Number of pages7
JournalThrombosis and Haemostasis
Volume65
Issue number5
Publication statusPublished - 1991
Externally publishedYes

Fingerprint

Hemophilia B
Factor IX
Point Mutation
Factor XIa
Codon
Genes
Exons
Enzyme Precursors
Prothrombin Time
Sequence Analysis
3'-(1-butylphosphoryl)adenosine
factor IX Nagoya 3
Calcium
Peptides
Mutation
DNA
Brain

ASJC Scopus subject areas

  • Hematology

Cite this

Hamaguchi, M., Matsushita, T., Tanimoto, M., Takahashi, I., Yamamoto, K., Sugiura, I., ... Saito, H. (1991). Three distinct point mutations in the factor IX gene of three Japanese CRM+ hemophilia B patients (factor IX B(M)Nagoya 2, factor IX Nagoya 3 and 4). Thrombosis and Haemostasis, 65(5), 514-520.

Three distinct point mutations in the factor IX gene of three Japanese CRM+ hemophilia B patients (factor IX B(M)Nagoya 2, factor IX Nagoya 3 and 4). / Hamaguchi, M.; Matsushita, T.; Tanimoto, M.; Takahashi, I.; Yamamoto, K.; Sugiura, I.; Takamatsu, J.; Ogata, K.; Kamiya, T.; Saito, H.

In: Thrombosis and Haemostasis, Vol. 65, No. 5, 1991, p. 514-520.

Research output: Contribution to journalArticle

Hamaguchi, M, Matsushita, T, Tanimoto, M, Takahashi, I, Yamamoto, K, Sugiura, I, Takamatsu, J, Ogata, K, Kamiya, T & Saito, H 1991, 'Three distinct point mutations in the factor IX gene of three Japanese CRM+ hemophilia B patients (factor IX B(M)Nagoya 2, factor IX Nagoya 3 and 4)', Thrombosis and Haemostasis, vol. 65, no. 5, pp. 514-520.
Hamaguchi, M. ; Matsushita, T. ; Tanimoto, M. ; Takahashi, I. ; Yamamoto, K. ; Sugiura, I. ; Takamatsu, J. ; Ogata, K. ; Kamiya, T. ; Saito, H. / Three distinct point mutations in the factor IX gene of three Japanese CRM+ hemophilia B patients (factor IX B(M)Nagoya 2, factor IX Nagoya 3 and 4). In: Thrombosis and Haemostasis. 1991 ; Vol. 65, No. 5. pp. 514-520.
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