DNA sequence analysis of three inhibitor-positive hemophilia B patients without gross gene deletion: Identification of four novel mutations in factor IX gene

Tadashi Matsushita, Mitsune Tanimoto, Koji Yamamoto, Isamu Sugiura, Motohiro Hamaguchi, Junki Takamatsu, Tadashi Kamiya, Hidehiko Saito

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Three hemophilia B patients with anti-factor IX antibodies who had no detectable gross deletion of the factor IX gene by Southern blotting analysis were investigated at the molecular level. All eight exons, accompanied by their splicing junction sites and presumptive promoter regions of the factor IX gene in these patients (total 5.5 kb in length) were amplified with the use of the polymerase chain reaction, followed by complete nucleotide sequence analysis. Three different types of novel single base substitutions and a 2 base-pair nucleotide deletion were identified. Patient HB-5 had two point mutations in his factor IX gene. One was located at the promoter region at nucleotide -793 and the other (C-to-T transition) was found in exon VI of the gene changing Gin-191 to a stop codon. Patient HB-6 had a point mutation (G-to-A) in the splice acceptor site, which interrupted the normal splicing of the last intron G. A small two-nucleotide deletion in exon III was detected in patient HB-7 and yielded frameshifted amino acids and terminated by a stop codon. These resuslts suggest that not only the gross gene deletion of factor IX gene but also the point mutations or small nucleotide deletion that may cause the interruption of coding informations for mature protein synthesis is predisposed to development of anti-factor IX inhibitors in patients with hemophilia B.

Original languageEnglish
Pages (from-to)487-491
Number of pages5
JournalJournal of Laboratory and Clinical Medicine
Volume116
Issue number4
Publication statusPublished - 1990
Externally publishedYes

Fingerprint

Hemophilia B
Factor IX
DNA sequences
Gene Deletion
DNA Sequence Analysis
Genes
Nucleotides
Mutation
Point Mutation
Exons
Terminator Codon
Genetic Promoter Regions
RNA Splice Sites
Polymerase chain reaction
Southern Blotting
Base Pairing
Introns
Sequence Analysis
Substitution reactions
Amino Acids

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

DNA sequence analysis of three inhibitor-positive hemophilia B patients without gross gene deletion : Identification of four novel mutations in factor IX gene. / Matsushita, Tadashi; Tanimoto, Mitsune; Yamamoto, Koji; Sugiura, Isamu; Hamaguchi, Motohiro; Takamatsu, Junki; Kamiya, Tadashi; Saito, Hidehiko.

In: Journal of Laboratory and Clinical Medicine, Vol. 116, No. 4, 1990, p. 487-491.

Research output: Contribution to journalArticle

Matsushita, T, Tanimoto, M, Yamamoto, K, Sugiura, I, Hamaguchi, M, Takamatsu, J, Kamiya, T & Saito, H 1990, 'DNA sequence analysis of three inhibitor-positive hemophilia B patients without gross gene deletion: Identification of four novel mutations in factor IX gene', Journal of Laboratory and Clinical Medicine, vol. 116, no. 4, pp. 487-491.
Matsushita, Tadashi ; Tanimoto, Mitsune ; Yamamoto, Koji ; Sugiura, Isamu ; Hamaguchi, Motohiro ; Takamatsu, Junki ; Kamiya, Tadashi ; Saito, Hidehiko. / DNA sequence analysis of three inhibitor-positive hemophilia B patients without gross gene deletion : Identification of four novel mutations in factor IX gene. In: Journal of Laboratory and Clinical Medicine. 1990 ; Vol. 116, No. 4. pp. 487-491.
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