Haemophilia in European royalty

Although an individual's haemophilia can usually be traced in the ancestry, in about 30% of cases there is no family history of the disorder, and the condition is speculated to be the result of spontaneous mutation in an ancestor.

[2] Victoria's appears to have been a spontaneous or de novo mutation, most likely inherited from one of her parents, and she is usually considered the source of the disease in modern cases of haemophilia among her descendants.

Queen Victoria's sons Edward VII, Alfred, Duke of Saxe-Coburg and Gotha, and Prince Arthur, Duke of Connaught and Strathearn were not haemophiliacs; however, her daughters Alice and Beatrice were confirmed carriers of the gene, and Victoria's son Leopold had haemophilia, making his daughter Princess Alice, Countess of Athlone a carrier as well.

Alice (1843–1878), Victoria's third child, and wife of the future Grand Duke Louis IV of Hesse and by Rhine (1837–1892), passed it on to at least three of her children: Irene, Friedrich, and Alix.

Leopold (1853–1884), Victoria's eighth child, was the first member of the family to manifest haemophilia; he died at age 30 from bleeding after a minor fall,[5] only two years after marrying Princess Helen of Waldeck and Pyrmont (1861–1922).

Beatrice (1857–1944), Victoria's ninth and last child, and wife of Prince Henry of Battenberg (1858–1896) passed it on to at least two, if not three, of her four children: No living member of the present or past reigning dynasties of Europe is known to have symptoms of haemophilia or is believed to carry the gene for it.

Using genetic analysis of the remains of the assassinated Romanov dynasty, and specifically Tsarevich Alexei, Rogaev et al. were able to determine that the "Royal Disease" is actually haemophilia B.

Specifically, they found a single-nucleotide change in the gene for clotting Factor IX that causes incorrect RNA splicing and produces a truncated, nonfunctional protein.