title: Genotype analysis identifies the cause of the "royal disease".
abstract: 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.
authors.affiliation: University of Massachusetts Medical School, 303 Belmont Street, Worcester, MA 01604, USA. Evgeny.Rogaev@umassmed.edu
authors.forename: Evgeny I
authors.initials: EI
authors.lastname: Rogaev
authors.forename: Anastasia P
authors.initials: AP
authors.lastname: Grigorenko
authors.forename: Gulnaz
authors.initials: G
authors.lastname: Faskhutdinova
authors.forename: Ellen L W
authors.initials: EL
authors.lastname: Kittler
authors.forename: Yuri K
authors.initials: YK
authors.lastname: Moliaka
mesh_terms: D000483:Alleles; D041321:Chromosomes, Human, X / Q000235:genetics; D018389:Codon, Nonsense; D005060:Europe; D005164:Factor IX / Q000235:genetics*; D005197:Famous Persons; D005260:Female; D050172:Genes, X-Linked; D005838:Genotype; D002836:Hemophilia B / Q000235:genetics* / Q000266:history; D006579:Heterozygote; D049672:History, 19th Century; D049673:History, 20th Century; D006801:Humans; D007438:Introns; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D012326:RNA Splicing
chemical_list: D018389:Codon, Nonsense; D005164:Factor IX