Severe hemophilia A in a female by cryptic translocation: Order and orientation of factor VIII within Xq28

Journal Article · Thu Apr 01 04:00:00 EST 1993 · Genomics; (United States)

DOI:https://doi.org/10.1006/geno.1993.1134· OSTI ID:6180032

Migeon, B R; McGinniss, M J; Antonarakis, S E; Axelman, J; Stasiowski, B A; Youssoufian, H; Kearns, W G; Chung, A; Pearson, P L; Kazazian, Jr, H H ^[1]; Muneer, R S ^[2]

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1. Johns Hopkins Univ., Baltimore, MD (United States)
2. Univ. of Oklahoma, Norman (United States)

The authors 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[prime] end of F8C, but left the more proximal G6PD locus intact on the der(17)chromosome. As the deleted segment includes the 5[prime] half of F8C as well as the subtelomeric DXYS64 locus, F8C must be oriented on the chromosome with its 5[prime] region closest to the telomere. Therefore, the order of these loci is Xcen-G6PD-3[prime]F8C-5[prime]F8C-DXYS64-Xqtel. The analysis of somatic cell hybrids has elucidated the true nature of the F8C mutation in the pro-band, 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. 27 refs., 5 figs., 1 tab.

• OSTI ID: 6180032
• Journal Information: Genomics; (United States), Journal Name: Genomics; (United States) Vol. 16:1; ISSN GNMCEP; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
BLOOD COAGULATION FACTORS
CHROMOSOMES
COAGULANTS
DISEASES
DNA HYBRIDIZATION
DNA SEQUENCING
DRUGS
GENE MUTATIONS
HEMATOLOGIC AGENTS
HEMIC DISEASES
HEMOPHILIA
HEREDITARY DISEASES
HETEROCHROMOSOMES
HUMAN CHROMOSOME 17
HUMAN CHROMOSOMES
HUMAN X CHROMOSOME
HYBRIDIZATION
MUTATIONS
ORGANIC COMPOUNDS
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
TRANSLOCATION
X CHROMOSOME