Genotype analysis identifies the cause of the "royal disease"

Science. 2009 Nov 6;326(5954):817. doi: 10.1126/science.1180660. Epub 2009 Oct 8.


The "royal disease," a blood disorder transmitted from Queen Victoria to European royal families, is a striking example of X-linked recessive inheritance. Although the disease is widely recognized to be a form of the blood clotting disorder hemophilia, its molecular basis has never been identified, and the royal disease is now likely extinct. We identified the likely disease-causing mutation by applying genomic methodologies (multiplex target amplification and massively parallel sequencing) to historical specimens from the Romanov branch of the royal family. The mutation occurs in F9, a gene on the X chromosome that encodes blood coagulation factor IX, and is predicted to alter RNA splicing and to lead to production of a truncated form of factor IX. Thus, the royal disease is the severe form of hemophilia, also known as hemophilia B or Christmas disease.

Publication types

  • Biography
  • Historical Article

MeSH terms

  • Alleles
  • Chromosomes, Human, X / genetics
  • Codon, Nonsense
  • Europe
  • Factor IX / genetics*
  • Famous Persons*
  • Female
  • Genes, X-Linked
  • Genotype
  • Hemophilia B / genetics*
  • Hemophilia B / history
  • Heterozygote
  • History, 19th Century
  • History, 20th Century
  • Humans
  • Introns
  • Male
  • Pedigree
  • Point Mutation*
  • RNA Splicing*


  • Codon, Nonsense
  • Factor IX

Personal name as subject

  • None Romanov family