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T296----M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.

Publication ,  Journal Article
Ketterling, RP; Bottema, CD; Koeberl, DD; Ii, S; Sommer, SS
Published in: Hum Genet
July 1991

By direct genomic sequencing, we have delineated the causative mutation in 64 families of European decent with hemophilia B. Six (9%) had a C----T transition at base 31008, which substitutes methionine for threonine 296 (T296----M) in the catalytic domain of factor IX. Five of the patients had the same haplotype (frequency of 16% in the northern European population). These individuals are of Amish/German descent and they are likely to share a common ancestor. The sixth patient had a different haplotype, which indicates that his mutation had an independent origin. The data highlight the importance of clinical criteria for the classification of hemophilia B. All six patients had clinically mild disease and their factor IX coagulant activities were in the range of 3%-6% when tested simultaneously in one laboratory, yet the factor IX activities provided with patient records varied 40-fold. Due to the high frequency of this mutation, we have utilized the technique of polymerase chain reaction amplification of specific alleles (PASA) to perform rapid and inexpensive carrier diagnoses in the families with this mutation. This is of particular importance for the Amish since the mutation should account for much of, if not all, the mild hemophilia B that is commonly found in this population.

Duke Scholars

Published In

Hum Genet

DOI

ISSN

0340-6717

Publication Date

July 1991

Volume

87

Issue

3

Start / End Page

333 / 337

Location

Germany

Related Subject Headings

  • Religion
  • Polymerase Chain Reaction
  • Pedigree
  • Mutation
  • Molecular Sequence Data
  • Male
  • Humans
  • Hemophilia B
  • Haplotypes
  • Genetics & Heredity
 

Citation

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Ketterling, R. P., Bottema, C. D., Koeberl, D. D., Ii, S., & Sommer, S. S. (1991). T296----M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection. Hum Genet, 87(3), 333–337. https://doi.org/10.1007/BF00200915
Ketterling, R. P., C. D. Bottema, D. D. Koeberl, S. Ii, and S. S. Sommer. “T296----M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.Hum Genet 87, no. 3 (July 1991): 333–37. https://doi.org/10.1007/BF00200915.
Ketterling, R. P., et al. “T296----M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.Hum Genet, vol. 87, no. 3, July 1991, pp. 333–37. Pubmed, doi:10.1007/BF00200915.
Journal cover image

Published In

Hum Genet

DOI

ISSN

0340-6717

Publication Date

July 1991

Volume

87

Issue

3

Start / End Page

333 / 337

Location

Germany

Related Subject Headings

  • Religion
  • Polymerase Chain Reaction
  • Pedigree
  • Mutation
  • Molecular Sequence Data
  • Male
  • Humans
  • Hemophilia B
  • Haplotypes
  • Genetics & Heredity