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 language | English |
|---|---|
| Pages (from-to) | 307-313 |
| Number of pages | 7 |
| Journal | Journal of Laboratory and Clinical Medicine |
| Volume | 112 |
| Issue number | 3 |
| Publication status | Published - 1988 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - DNA analysis of seven patients with hemophilia B who have anti-factor IX antibodies
T2 - Relationship to clinical manifestations and evidence that the abnormal gene was inherited.
AU - Tanimoto, M.
AU - Kojima, T.
AU - Kamiya, T.
AU - Takamatsu, J.
AU - Ogata, K.
AU - Obata, Y.
AU - Inagaki, M.
AU - Iizuka, A.
AU - Nagao, T.
AU - Kurachi, K.
AU - Saito, H.
PY - 1988
Y1 - 1988
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0023690878&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023690878&partnerID=8YFLogxK
M3 - Article
C2 - 3411192
AN - SCOPUS:0023690878
VL - 112
SP - 307
EP - 313
JO - Translational Research
JF - Translational Research
SN - 1931-5244
IS - 3
ER -