ANDRZEJ KRAUZEIn the late 1990s, a hematologist in Texas approached Dianna Milewicz with a problem. One of his patients had a rare bleeding disorder that could not be explained, and a clinical assessment of the patient’s family members revealed that several of them also had it. The initial patient had required a blood transfusion as a toddler after falling down, and again at age 12 when he had a tooth removed. When his sister had lost baby teeth, her gums had to be packed with gauze to soak up the excessive bleeding. Childbirth was extremely dangerous, and doctors refused to perform elective surgery on some family members for fear of fatal bleeds. “They tried numerous treatments,” says Milewicz, a medical geneticist at the University of Texas Health Science Center at Houston. “But nothing seemed to help very much in this family.”
Milewicz agreed to investigate what came to be known as the East Texas bleeding disorder, and she obtained blood samples from 16 family members affected by the disorder and 13 who were unaffected. The family did not want to be interviewed or identified. Through a linkage analysis, Milewicz and her colleagues focused on a region of chromosome 1 that contained the gene for a coagulation factor called factor V (FV).
The variant they identified in the gene seemed like a great lead, given FV’s crucial role in developing blood clots. But when they took a closer look, they found that the resulting amino acid change was in a portion of the protein that gets cleaved off from a precursor of FV before it becomes active ...
