The Royal Disease
During the winter of 1884, Queen Victoria's youngest son, Prince Leopold, was convalescing in France. While there, he slipped and fell and couldn't stop bleeding. Within a few hours, he died. Prince Leopold was the first monarch known to suffer from hemophilia—a blood disorder that causes excessive bleeding. It appears Victoria was responsible for the spread of the "royal disease" among monarchs across Europe (her relatives in Russia, Spain, France and Germany all had the disease).
There are several versions of the disease, but no one knew what type Victoria carried and this strain is now extinct. Evgeny Rogaev from the University of Massachusetts was curious about Victoria—she is particularly interesting because none of her ancestors carried the gene, and scientists believed the Queen suffered from a spontaneous mutation. Using the remains of the Romanov family (Czar Nicholas II and Czarina Alexandra's children are Victoria's great grandchildren), researchers examined DNA to learn more.
Publishing the results in the journal Science, Rogaev notes that Victoria and her descendants suffered from a rare and severe form of hemophilia B, or Christmas disease. Using multiplex target amplification and parallel sequencing, Rogaev and his colleagues noticed a mutation on the F9 gene on the X chromosome, which controls the blood clotting agent, Factor IX, and can alter RNA splicing. This mutation matches those found in hemophilia B. Women generally only carry the mutation on one of their X chromosomes, meaning they rarely suffer from the disease and most often pass it on to their male descendants. Those male descendants do suffer from the disease, because it expresses itself on their only X chromosome.