title: Molecular characterization of hemophilia B in North Indian families: identification of novel and recurrent molecular events in the factor IX gene.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Functional Genomics Unit, Institute of Genomics and Integrative Biology, CSIR, Delhi, India.
authors.forename: Anubha
authors.initials: A
authors.lastname: Mahajan
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Chavali
authors.forename: Madhulika
authors.initials: M
authors.lastname: Kabra
authors.forename: Madhumita Roy
authors.initials: MR
authors.lastname: Chowdhury
authors.forename: Dwaipayan
authors.initials: D
authors.lastname: Bharadwaj
mesh_terms: D019943:Amino Acid Substitution; D020137:Base Pair Mismatch; D041321:Chromosomes, Human, X / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005164:Factor IX / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006580:Genetic Carrier Screening; D018740:Genetic Heterogeneity; D002836:Hemophilia B / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D020125:Mutation, Missense; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: D022821:RNA Splice Sites; D005164:Factor IX