Severe Hemophilia A in a Female by Cryptic Translocation

Order and Orientation of Factor VIII within Xq28

Barbara R Migeon, Matthew J. McGinniss, Stylianos E. Antonarakis, Joyce Axelman, Beth A. Stasiowski, Hagop Youssoufian, William G. Kearns, Alice Chung, Peter L. Pearson, Haig Kazazian, Razia S. Muneer

Research output: Contribution to journalArticle

Abstract

We report studies of a female with severe hemophilia A resulting from a complex de novo translocation of chromosomes X and 17 (46,X,t(X;17)). Somatic cell hybrids containing the normal X, the der(X), or the der(17) were analyzed for coagulation factor VIII (F8C) sequences using Southern blots and polymerase chain reaction. The normal X, always late replicating, contains a normal F8C gene, whereas the der(X) has no F8C sequences. The der(17) chromosome containing Xq24-Xq28 carries a functional G6PD locus and a deleted F8C allele that lacks exons 1-15. Also, it lacks the DXYS64-X locus, situated between the F8C locus and the Xq telomere. These results indicate that a cryptic breakpoint within Xq28 deleted the 5′ end of F8C, but left the more proximal G6PD locus intact on the der(17) chromosome. As the deleted segment includes the 5′ half of F8C as well as the subtelomeric DXYS64 locus, F8C must be oriented on the chromosome with its 5′ region closest to the telomere. Therefore, the order of these loci is Xcen-G6PD-3′F8C-5′F8C-DXYS64-Xqtel. The analysis of somatic cell hybrids has elucidated the true nature of the F8C mutation in the proband, revealing a more complex rearrangement (three chromosomes involved) than that expected from cytogenetic analysis, chromosome painting, and Southern blots. A 900-kb segment within Xq28 has been translocated to another autosome. Hemophilia A in this heterozygous female is due to the decapitation of the F8C gene on the der(17) and inactivation of the intact allele on the normal X.

Original languageEnglish (US)
Pages (from-to)20-25
Number of pages6
JournalGenomics
Volume16
Issue number1
DOIs
StatePublished - Apr 1993

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Chromosomes, Human, Pair 17
Factor VIII
Hemophilia A
Hybrid Cells
Telomere
Southern Blotting
Chromosomes
Alleles
Chromosome Painting
Decapitation
Cytogenetic Analysis
Genes
Exons
Polymerase Chain Reaction
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

Migeon, B. R., McGinniss, M. J., Antonarakis, S. E., Axelman, J., Stasiowski, B. A., Youssoufian, H., ... Muneer, R. S. (1993). Severe Hemophilia A in a Female by Cryptic Translocation: Order and Orientation of Factor VIII within Xq28. Genomics, 16(1), 20-25. https://doi.org/10.1006/geno.1993.1134

Severe Hemophilia A in a Female by Cryptic Translocation : Order and Orientation of Factor VIII within Xq28. / Migeon, Barbara R; McGinniss, Matthew J.; Antonarakis, Stylianos E.; Axelman, Joyce; Stasiowski, Beth A.; Youssoufian, Hagop; Kearns, William G.; Chung, Alice; Pearson, Peter L.; Kazazian, Haig; Muneer, Razia S.

In: Genomics, Vol. 16, No. 1, 04.1993, p. 20-25.

Research output: Contribution to journalArticle

Migeon, BR, McGinniss, MJ, Antonarakis, SE, Axelman, J, Stasiowski, BA, Youssoufian, H, Kearns, WG, Chung, A, Pearson, PL, Kazazian, H & Muneer, RS 1993, 'Severe Hemophilia A in a Female by Cryptic Translocation: Order and Orientation of Factor VIII within Xq28', Genomics, vol. 16, no. 1, pp. 20-25. https://doi.org/10.1006/geno.1993.1134
Migeon, Barbara R ; McGinniss, Matthew J. ; Antonarakis, Stylianos E. ; Axelman, Joyce ; Stasiowski, Beth A. ; Youssoufian, Hagop ; Kearns, William G. ; Chung, Alice ; Pearson, Peter L. ; Kazazian, Haig ; Muneer, Razia S. / Severe Hemophilia A in a Female by Cryptic Translocation : Order and Orientation of Factor VIII within Xq28. In: Genomics. 1993 ; Vol. 16, No. 1. pp. 20-25.
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