After the remains of two individuals were discovered in the Ural Mountains, Rogaev analyzed fragments of bone and traced the genetic lineage back to the same immediate Romanov family. It wasn't, however, hemophilia B that killed the Russian prince and his sister-likely Anastasia-rumored to have escaped the Bolshevik revolutionaries who assassinated the other Romanovs in 1918. Hemophilia A is a clotting factor VIII deficiency (factor VIII assists with blood coagulation), while hemophilia B is a clotting factor IX deficiency (factor IX is an enzyme in the coagulation system). They found a mutation that would have led to an "abnormal splicing site" on the factor IX gene, a tale-tell sign of hemophilia B, which is far more rare than hemophilia A and now appears to be extinct in the European royal lines. Using sequencing and amplification techniques, the investigators were able to obtain gene sequences from the 91-year-old material. The authors of the new study, led by Evgeny Rogaev of the University of Massachusetts Medical School and Lomonosov Moscow State University in Russia, sampled bones found in the Ural Mountains in 2007 now known to belong to the son of Russian Empress Alexandra (Victoria's granddaughter), Crown Prince Alexei, and one of his sisters. Those who manifest the disease often have excessive bleeding, as the blood does not properly coagulate, which can lead to pain and even death. It is also recessive and is more commonly exhibited in males, causing it to go undetected in many carriers, who may pass it on to future generations. Hemophilia is caused by a mutation-likely spontaneous in Victoria's case-on the X chromosome and can be passed along the maternal line of families. The family apparently suffered from a very rare form of hemophilia, indeed. Research published online today in Science sheds some light on the mystery thanks to advances in genetic research and the 2007 discovery of some long-lost Russian remains. But it has remained unknown precisely what variety of the disease afflicted the family and how many deceased relatives may have had the inherited disease. Queen Victoria and many of her descendants carried what was once called "Royal disease"-now known as hemophilia, a blood clotting disorder.
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