Genotype analysis identifies the cause of the “Royal Disease”

University of Massachusetts Medical School, 303 Belmont Street, Worcester, MA 01604, USA.
Science (Impact Factor: 31.48). 10/2009; 326(5954):817. DOI: 10.1126/science.1180660
Source: PubMed

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.

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