DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies: Relationship to clinical manifestations and evidence that the abnormal gene was inherited.

M. Tanimoto, T. Kojima, T. Kamiya, J. Takamatsu, K. Ogata, Y. Obata, M. Inagaki, A. Iizuka, T. Nagao, K. Kurachi, H. Saito

Research output: Contribution to journalArticle

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Abstract

We have investigated genomic DNA samples of 24 patients with hemophilia B (factor IX deficiency), including seven patients with anti-factor IX antibodies (inhibitors), by molecular probes. Seventeen patients without inhibitors against factor IX and three patients with inhibitor showed no abnormalities in their restriction fragments generated by digestions of the genomic DNA by BamHI, EcoRI, MspI, or TaqI and hybridized with a factor IX cDNA probe (pHFIX). The remaining four patients with inhibitors were found to have gross deletions of the factor IX gene. Among those four patients, two were from the same family. Quantitative Southern blotting clearly showed that the abnormal gene was inherited in this family. DNA from the mother of another patient with deletion of the factor IX gene showed normal gene dosage, indicating that the mutation must have occurred at the mother's germ cells. The genomic DNA samples of four patients with gross factor IX gene deletions were found to lack the entire factor IX gene as analyzed with a factor IX cDNA as well as with a 3'-genomic factor IX fragment as probes. The hypoxanthine phosphoribosyltransferase (HPRT) gene probe, however, was found to hybridize with all of these DNA samples, indicating that the deletions in these genomic DNA samples had not extended to the region containing the HPRT gene locus in q27 proximal to the factor IX gene locus on the X chromosome. Several clinical characteristics were compared between inhibitor cases with gene deletion and inhibitor cases without obvious gene deletion. There were no apparent differences in the two groups as to the age of diagnosis of hemophilia B, the age of inhibitor detection, the titer of inhibitors, and the intensity of replacement therapy before the development of inhibitors.

Original languageEnglish
Pages (from-to)307-313
Number of pages7
JournalJournal of Laboratory and Clinical Medicine
Volume112
Issue number3
Publication statusPublished - 1988
Externally publishedYes

Fingerprint

Hemophilia B
Factor IX
Genes
Antibodies
DNA
Gene Deletion
Hypoxanthine Phosphoribosyltransferase
Complementary DNA
Molecular Probes
Gene Dosage
X Chromosome
Southern Blotting
Germ Cells
Chromosomes
Digestion
Stem Cells
Mothers
Cells

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies : Relationship to clinical manifestations and evidence that the abnormal gene was inherited. / Tanimoto, M.; Kojima, T.; Kamiya, T.; Takamatsu, J.; Ogata, K.; Obata, Y.; Inagaki, M.; Iizuka, A.; Nagao, T.; Kurachi, K.; Saito, H.

In: Journal of Laboratory and Clinical Medicine, Vol. 112, No. 3, 1988, p. 307-313.

Research output: Contribution to journalArticle

Tanimoto, M, Kojima, T, Kamiya, T, Takamatsu, J, Ogata, K, Obata, Y, Inagaki, M, Iizuka, A, Nagao, T, Kurachi, K & Saito, H 1988, 'DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies: Relationship to clinical manifestations and evidence that the abnormal gene was inherited.', Journal of Laboratory and Clinical Medicine, vol. 112, no. 3, pp. 307-313.
Tanimoto, M. ; Kojima, T. ; Kamiya, T. ; Takamatsu, J. ; Ogata, K. ; Obata, Y. ; Inagaki, M. ; Iizuka, A. ; Nagao, T. ; Kurachi, K. ; Saito, H. / DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies : Relationship to clinical manifestations and evidence that the abnormal gene was inherited. In: Journal of Laboratory and Clinical Medicine. 1988 ; Vol. 112, No. 3. pp. 307-313.
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abstract = "We have investigated genomic DNA samples of 24 patients with hemophilia B (factor IX deficiency), including seven patients with anti-factor IX antibodies (inhibitors), by molecular probes. Seventeen patients without inhibitors against factor IX and three patients with inhibitor showed no abnormalities in their restriction fragments generated by digestions of the genomic DNA by BamHI, EcoRI, MspI, or TaqI and hybridized with a factor IX cDNA probe (pHFIX). The remaining four patients with inhibitors were found to have gross deletions of the factor IX gene. Among those four patients, two were from the same family. Quantitative Southern blotting clearly showed that the abnormal gene was inherited in this family. DNA from the mother of another patient with deletion of the factor IX gene showed normal gene dosage, indicating that the mutation must have occurred at the mother's germ cells. The genomic DNA samples of four patients with gross factor IX gene deletions were found to lack the entire factor IX gene as analyzed with a factor IX cDNA as well as with a 3'-genomic factor IX fragment as probes. The hypoxanthine phosphoribosyltransferase (HPRT) gene probe, however, was found to hybridize with all of these DNA samples, indicating that the deletions in these genomic DNA samples had not extended to the region containing the HPRT gene locus in q27 proximal to the factor IX gene locus on the X chromosome. Several clinical characteristics were compared between inhibitor cases with gene deletion and inhibitor cases without obvious gene deletion. There were no apparent differences in the two groups as to the age of diagnosis of hemophilia B, the age of inhibitor detection, the titer of inhibitors, and the intensity of replacement therapy before the development of inhibitors.",
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AU - Kamiya, T.

AU - Takamatsu, J.

AU - Ogata, K.

AU - Obata, Y.

AU - Inagaki, M.

AU - Iizuka, A.

AU - Nagao, T.

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AU - Saito, H.

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