Genotype Analysis Identifies the Cause of the “Royal Disease”

  title={Genotype Analysis Identifies the Cause of the “Royal Disease”},
  author={Evgeny I. Rogaev and Anastasia P. Grigorenko and Gulnaz Faskhutdinova and Ellen L. W. Kittler and Yuri K. Moliaka},
  pages={817 - 817}
The "royal disease," a blood disorder transmitted from Queen Victoria to European royal families, is a striking example of X-linked recessive inheritance. [...] Key Method 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…Expand
Christmas disease in a Hovawart family resembling human hemophilia B Leyden is caused by a single nucleotide deletion in a highly conserved transcription factor binding site of the F9 gene promoter
Evidence is provided that the deletion in the Hovawart family caused a rare type of hemophilia B resembling human hemophiles B Leyden. Expand
Christmas disease in a Hovawart family resembling human hemophilia B Leyden is caused by a single nucleotide deletion in a highly conserved transcription factor binding site of the F9 gene promoter
Evidence is provided that the deletion identified in the Hovawart family caused a rare type of hemophilia B resembling human hemophile B Leyden, caused by nucleotide variants in important developmental and hormone-responsive regulatory regions of the factor IX gene promoter interfering with transcription factor binding. Expand
The ‘royal disease’– haemophilia A or B? A haematological mystery is finally solved
  • N. Lannoy, C. Hermans
  • Medicine
  • Haemophilia : the official journal of the World Federation of Hemophilia
  • 2010
Following a scientific approach combining current genetic experimentation tools and the development of biological information technology, researchers were able to identify each body, and obtain precious genetic material from the young Czar Alexis, who was stricken by the disease, which revealed a causal substitution in the splice acceptor site of exon 4 in the F9 gene. Expand
Hemophilia B Leyden and once mysterious cis-regulatory mutations.
The human F9 promoter is presented as a model example for which saturation mutation mapping has revealed the mechanisms of its regulation and it is suggested that the growing number of genome-wide studies of transcription factor activity will accelerate both the discovery and understanding of regulatory polymorphisms and mutations. Expand
Delineating the Hemostaseome as an aid to individualize the analysis of the hereditary basis of thrombotic and bleeding disorders
The Hemostaseome is examined, a prerequisite for a study of the nature of the genetic variants that may cause disease in individuals whose hemostatic balance has become shifted toward either a prothrombotic or anticoagulant phenotype, by narrowing the focus from an entire genome to that of a single biological system. Expand
Heterogeneous lengths of copy number mutations in human coagulopathy revealed by genome-wide high-density SNP array
This study revealed unexpectedly heterogeneous lengths of copy number mutations underlying human coagulopathy, and single nucleotide polymorphism-array had limitations in detectingcopy number mutations involving a single exon or those of a gene with homologous sequences such as a pseudogene. Expand
A CpG mutational hotspot in a ONECUT binding site accounts for the prevalent variant of hemophilia B Leyden.
These findings establish ONECUT transcription factors as the missing hemophilia B Leyden regulators that operate through the -5/-6 site. Expand
High-throughput molecular diagnosis of von Willebrand disease by next generation sequencing methods
This is one of the first reports in which this technology has been shown to be feasible for large-scale mutation screening by single gene re-sequencing for von Willebrand disease. Expand
Causal Varian discovery in Familial Congenital Heart Disease - An Integrative -Omic Approach
A rare, novel mutation in the LAMA4 gene carried by the proband and other family members may contribute to the development of Hypoplastic left heart syndrome in this family. Expand
Improved understanding of the disorder and development of efficacious therapy based on prophylactic replacement of the missing factor has caused a paradigm shift, and today individuals with haemophilia can look forward to a virtually normal life expectancy and quality of life. Expand


Genomic identification in the historical case of the Nicholas II royal family
It is demonstrated that convergent analysis of complete mitochondrial genome sequences combined with nuclear DNA profiles is an efficient and conclusive method for individual and kinship identification of specimens obtained from old historic relics. Expand
  • R. Stevens
  • Medicine
  • British journal of haematology
  • 1999
The scientific evidence regarding the remains seems overwhelming, but the historical drama continues, and there is even now a possibility that the mystery may be solved. Expand
Historical and political implications of haemophilia in the Spanish royal family
The political implications of haemophilia in the marriage of King Alfonso XIII of Spain and Princess Victoria Eugenie Battenberg of England have been reviewed and it can be said that when the disease affected a royal couple, the political consequences were great. Expand
Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis.
Definitions in Hemophilia - Recommendation of the Scientific Subcommittee on Factor VIII and Factor IX of the Scientific and Standardization Committee of the International Society on Thrombosis andExpand
Materials and methods are available as supporting material on Science Online
    Mironov for bioinformatics; and A. Chikunov for general support
      Single-letter abbreviations for the amino acid residues are as follows
        Tazetdinov for technical support; V. Gromov аnd N. Nevolin for assistance with the bone samples