Variation of the non-factor VIII sequences detected by a probe from intron 22 of the factor VIII gene

A severe hemophilia A family has been studied with the factor VIII (F.VIII) intragenic XbaI polymorphism. During this investigation, a new variant hybridization pattern was observed with important implications concerning the non-F.VIII DNA sequences detected by the probe from intron 22, p482.6. Both Southern hybridization studies and direct analysis of amplified DNA demonstrated a variant form of the non-F.VIII sequences. This variant DNA sequence has not been responsible for any detectable phenotypic abnormalities, and likely represents a polymorphic change. In conclusion, this study has shown that the non- F.VIII sequences detected with the probe p482.6 are situated on the X chromosome, they seem to be present in two copies, and either or both copies infrequently possess a polymorphic XbaI site or a partial deletion.

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Variation of the non-factor VIII sequences detected by a probe from intron 22 of the factor VIII gene

Blood ◽

10.1182/blood.v75.1.139.139 ◽

1990 ◽

Vol 75 (1) ◽

pp. 139-143 ◽

Cited By ~ 9

Author(s):

DP Lillicrap ◽

SA Taylor ◽

PC Schuringa ◽

VS Blanchette ◽

JK Lovsted ◽

...

Keyword(s):

Factor Viii ◽

Dna Sequences ◽

Southern Hybridization ◽

Hemophilia A ◽

Direct Analysis ◽

Variant Form ◽

Partial Deletion ◽

Factor Viii Gene ◽

New Variant ◽

Xbai Polymorphism

Abstract A severe hemophilia A family has been studied with the factor VIII (F.VIII) intragenic XbaI polymorphism. During this investigation, a new variant hybridization pattern was observed with important implications concerning the non-F.VIII DNA sequences detected by the probe from intron 22, p482.6. Both Southern hybridization studies and direct analysis of amplified DNA demonstrated a variant form of the non-F.VIII sequences. This variant DNA sequence has not been responsible for any detectable phenotypic abnormalities, and likely represents a polymorphic change. In conclusion, this study has shown that the non- F.VIII sequences detected with the probe p482.6 are situated on the X chromosome, they seem to be present in two copies, and either or both copies infrequently possess a polymorphic XbaI site or a partial deletion.

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Faculty Opinions recommendation of AAV5-Factor VIII Gene Transfer in Severe Hemophilia A.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732279394.793544825 ◽

2018 ◽

Author(s):

Valder Arruda ◽

Ben Samelson-Jones

Keyword(s):

Gene Transfer ◽

Factor Viii ◽

Hemophilia A ◽

Severe Hemophilia ◽

Factor Viii Gene

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Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.88.16.7405 ◽

1991 ◽

Vol 88 (16) ◽

pp. 7405-7409 ◽

Cited By ~ 87

Author(s):

M. Higuchi ◽

H. H. Kazazian ◽

L. Kasch ◽

T. C. Warren ◽

M. J. McGinniss ◽

...

Keyword(s):

Factor Viii ◽

Molecular Characterization ◽

Hemophilia A ◽

Severe Hemophilia ◽

Factor Viii Gene ◽

Coding Regions ◽

Splice Junctions

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THE RELATIVE EFFICACY OF GENETIC ANALYSIS AND COAGULATION TESTING IN THE DIAGNOSIS OF CARRIERS OF HEMOPHILIA A

10.1055/s-0038-1644010 ◽

1987 ◽

Author(s):

D Lillicrap ◽

A R Giles ◽

J J A Holden ◽

B N White

Keyword(s):

Factor Viii ◽

Gene Deletion ◽

Hemophilia A ◽

Fragment Length Polymorphism ◽

Genetic Diagnosis ◽

Prior History ◽

Carrier Status ◽

Factor Viii Gene ◽

Coagulation Testing ◽

History Of

This study has assessed the relative benefits of restriction fragment length polymorphism (RFLP) linkage and coagulation testing in the diagnosis of carriers of hemophilia A. 221 samples from 55 families have been studied for intragenic and flanking RFLPs. All samples were tested for the Factor VIII intragenic Bell RFLP and for the flanking marker St 14. 83% of obligate carrier females were heterozygous at oneor both of these two polymorphicsites. However, only38% of these women were heterozygous at the intragenic site and might safely be offered prenatal diagnosis using this marker for the hemophilia mutation. Carrier diagnosis was obtained in 52% of 81 potential carriers tested. Diagnosis wasbased on intragenic RFLP information in only 48% of these cases. Genetic diagnosis was possible in 27 atrisk women from families with no prior history of hemophilia. Four of these women were diagnosed as carriers on the basis of a gross Factor VIII gene deletion and the remaining 23 women were identified as non-carriers by the Bell (11) and Stl4 (12) RFLP data. 39 women remained undiagnosed after gene analysis studies. 23 of these women were female relatives of sporadic hemophiliacs and thus RFLP segregation analysis was inappropriate. A further 9 potential carriers were undiagnosed because of homozygosity in key individuals in their families. In 31 potential carriers we have quantitated Factor VIII:C (one stage assay) and vWf:Ag (Laurell and ELISA) and derived probabilities for carrier status. In 3 women there was conflicting genetic and coagulation data. Meanwhile, in 12 undiagnosed women from sporadic families, carrier diagnostic probabilities of > 0.9 were obtained. These studies indicate that optimal carrier detection for hemophilia A requires more intragenic and closely linked RFLPs and the continuance of coagulation testing to assist women from sporadic families.

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