Novel mutations in factor IX gene from western India with reference to their phenotypic and haplotypic attributes

J Pediatr Hematol Oncol. 2009 Mar;31(3):157-60. doi: 10.1097/MPH.0b013e31818b3759.


Background: Hemophilia B (HB) is an X-linked recessively inherited bleeding disorder caused by heterogeneous mutations in the factor IX gene.

Study design and methods: We screened for mutations in HB patients using a combination of multiplex polymerase chain reaction, conformation sensitive gel electrophoresis, and DNA sequencing. Phenotypic analysis was performed using 1 stage assay for factor IX: C activity and enzyme-linked immunosorbent assay for factor IX: Ag. Haplotype analysis was performed using the common polymorphic markers of the factor IX gene.

Results: Seventeen novel mutations comprising of missense mutations, nonsense mutations, and small deletions were detected. Haplotype analysis indicated that some of the patients had a common haplotype background but had different molecular defects thereby suggesting that all the mutations arose de novo. Phenotypic data suggested that about one-fourth of the patients (23%) had antigen-activity discordance. Furthermore, it was observed that a majority of the molecular defects (71%) were located in exon H of the factor IX gene. The mutation screening strategy was thus modified wherein exon H was screened first followed by screening of other exons.

Conclusions: The present findings suggest that there is a wide phenotypic and genotypic heterogeneity in HB. Presence of more than 70% of mutations in exon H of the factor IX gene allows us to adopt a cost effective screening strategy in offering genetic diagnosis to the affected families.

MeSH terms

  • DNA Mutational Analysis
  • Enzyme-Linked Immunosorbent Assay
  • Exons / genetics
  • Factor IX / genetics*
  • Genetic Testing / economics
  • Genetic Testing / methods*
  • Haplotypes
  • Hemophilia B / genetics*
  • Humans
  • India
  • Mutation
  • Phenotype
  • Polymerase Chain Reaction


  • Factor IX