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Hemophilia A is an X-linked recessive disease. This fetus has a 25% chance of inheriting hemophilia A. From the pedigree shown in Figure A, we know that the pregnant woman's (black arrow) mother is a carrier (as the pregnant woman's maternal grandfather and brother both have the disease). The pregnant woman thus has a 50% chance of being a carrier for hemophilia A (she inherited 1 X chromosome from her mother, who is a known carrier). In turn, the pregnant woman has a 50% chance of passing on the affected X chromosome to her son. Multiplying the 2 probabilities, (0.5*0.5=.25) gives a 25% chance that the pregnant woman's male fetus will have hemophilia A. Ballas et al. discuss the diagnostic work-up for bleeding disorders, including hemophilia A. An extremely thorough family history, in conjunction with a physical examination, is the most important tool. Specific laboratory work and tests are secondary. Dobyns et al. review the nature of X-linked disease, and argue that many times the inheritance is not truly 'dominant' or 'recessive'. Many X-linked disorders have variable expressivity due to such mechanisms in females as cell autonomous expression, skewed X-inactivation, clonal expansion, or somatic mosaicism. Figure A is a pedigree of an X-linked recessive disease. Illustration A shows the probabilities associated with X-linked inheritance; note the male has a 50% chance of inheriting the disease only when the mother is a known carrier. Illustration B summarizes the outcomes when the father is affected with an X-linked recessive disease. Incorrect Answers: Answers 1,3,4,5: Per the calculations above, the male fetus has a 25% chance of having hemophilia A.
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