Identification of a single nucleotide C-to-T transition and five different deletions in patients with severe hemophilia B

• Published in: American journal of human genetics Vol. 45; no. 1; pp. 115 - 122
• Main Authors: LUDWIG, M, SCHWAAB, R, EIGEL, A, HORST, J, EGLI, H, BRACKMAN, H.-H, OLEK, K
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01.07.1989
• Subjects: Biological and medical sciences; Chromosome Deletion; Cytosine; DNA - blood; DNA - genetics; Factor IX - genetics; Female; Genes; Hematologic and hematopoietic diseases; Hemophilia A - genetics; Humans; Male; Medical sciences; Mutation; Pedigree; Platelet diseases and coagulopathies; Reference Values; Restriction Mapping; Thymine; Chromosomal aberration; Human; Molecular hybridization; Nucleotide sequence; Partial deletion; Hemophilia B; Hemopathy; Factor IX; Restriction fragment length polymorphism; DNA; Abnormal chromosome; Mutation; Southern blotting; Coagulopathy
• ISSN: 0002-9297; 1537-6605

DNA of 70 unrelated hemophilia B patients, including three inhibitor patients, was analyzed by using various restriction enzymes and was hybridized with both a factor IX cDNA and 3'- and 5'-flanking probes. When the gene was mapped this way, six patients all afflicted with severe hemophilia B were shown to have a deviating hybridization pattern. One inhibitor patient showed a partial deletion of about 9 kb that removes exons a-c. A partial deletion of at least 11 kb that removed exon a and that had a maximum size of 35 kb in the 5'-flanking region could be identified in a patient of unknown status. In another three noninhibitor patients a complete deletion of the factor IX gene and two partial deletions could be observed. The partial deletions are of approximately 8 kb and approximately 1.5 kb, removing exons d and e and exon g, respectively. As detected by oligonucleotide probing, a C-to-T transition at amino acid 338 gave rise to an altered TaqI restriction pattern that could be observed in a sixth patient. The other 64 hemophilia B patients, including two inhibitor patients, showed a hybridization pattern indistinguishable from a normal one.