Molecular characterization of hemophilia B in North Indian families: identification of novel and recurrent molecular events in the factor IX gene

Haematologica. 2004 Dec;89(12):1498-503.


Background and objectives: Hemophilia B is an X-linked recessive, bleeding disorder caused by mutations in the factor IX gene. A wide range of mutations, showing large molecular heterogeneity, has been described in hemophilia B patients. Our study was aimed at characterizing mutations in the factor IX gene in a cohort of North Indian hemophilia B patients.

Design and methods: Polymerase chain reaction (PCR) amplification and direct sequencing of all regions of likely functional significance- the coding regions, promoter, the 5' UTR, the splice junctions and parts of the 3' UTR of the factor IX gene was done in 18 families carrying a severe form of hemophilia B.

Results: We identified 10 point mutations (including 2 novel ones); one novel deletion and one donor splice site mutation. Recurrence of a nonsense and a missense mutation was observed. The mutation in 3 families could not be characterized. None of the 14 polymorphic positions reported in the Haemophilia B Mutation database in the regions sequenced were polymorphic; herein we report four novel synonymous single base mismatches. One mutation reported to be causative in the database was found to be more likely a non-causal polymorphism.

Interpretation and conclusions: Our data confirm the remarkable heterogeneity of the mutational spectrum in hemophilia B among affected families. This is the first mutation report on the disease in the Indo-Aryan population from the Indian subcontinent. Identification of a causative mutation leads to more precise carrier detection than does conventional polymorphism-based linkage analysis. This can effectively be used to establish genotype/ phenotype relationships.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Base Pair Mismatch
  • Chromosomes, Human, X / genetics
  • DNA Mutational Analysis
  • Exons / genetics
  • Factor IX / genetics*
  • Female
  • Frameshift Mutation
  • Genetic Carrier Screening
  • Genetic Heterogeneity
  • Hemophilia B / ethnology
  • Hemophilia B / genetics*
  • Humans
  • India / epidemiology
  • Male
  • Mutation, Missense
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Protein Structure, Tertiary / genetics
  • RNA Splice Sites / genetics
  • Sequence Analysis, DNA
  • Sequence Deletion


  • RNA Splice Sites
  • Factor IX

Associated data

  • OMIM/306900