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

Journal Article · Thu Aug 15 00:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.16.7405· OSTI ID:5602392

Higuchi, Miyoko; Kazazian, Jr, H H; Kasch, L; Warren, T C; McGinniss, M J; Antonarakis, S E ^[1]; Phillips, III, J A; Janco, R ^[2]; Kasper, C ^[3]

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1. Johns Hopkins Univ., Baltimore, DM (United States)
2. Vanderbilt Univ., Nashville, TN (United States)
3. Orthopedic Hospital, Los Angeles, CA (United States)

Hemophilia A is an X chromosome-linked disorder resulting from deficiency of factor VIII, an important protein in blood coagulation. A large number of disease-producing mutations have been reported in the factor VIII gene. However, a comprehensive analysis of the mutations has been difficult because of the larger gene size, its many scattered exons, and the high frequency of de novo mutations. Recently, the authors have shown that nearly all mutations resulting in mild-to-moderate hemophilia A can be detected by PCR and denaturing gradient gel electrophoresis (DGGE). In this study, they attempted to discover the mutations causing severe hemophilia A by analyzing 47 unselected patients, 30 of whom had severe hemophilia and 17 of whom had mild-to-moderate disease. Using DGGE as a screening method, they analyzed 99% of the coding region, 94% of the splice junctions, the promoter region, and the polyadenylylation site of the gene. They found the mutation in 16 of 17 (94%) patients with mild-to-moderate disease but in only 16 of 30 (53%) patients with severe hemophilia A.

• OSTI ID: 5602392
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:16; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GENE MUTATIONS
DNA SEQUENCING
HEREDITARY DISEASES
MOLECULAR BIOLOGY
HUMAN X CHROMOSOME
GENETIC MAPPING
BLOOD COAGULATION
BLOOD COAGULATION FACTORS
ELECTROPHORESIS
GENE AMPLIFICATION
HEMOPHILIA
PATIENTS
CHROMOSOMES
COAGULANTS
DISEASES
DRUGS
HEMATOLOGIC AGENTS
HEMIC DISEASES
HETEROCHROMOSOMES
HUMAN CHROMOSOMES
MAPPING
MUTATIONS
ORGANIC COMPOUNDS
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
X CHROMOSOME
550400* - Genetics