A Family with a Bleeding Disorder
A family is referred to a clinic. The father has a mild bleeding tendency; his daughter has prolonged bleeding after a tooth extraction; his son has no symptoms. Clotting tests show the father and daughter have reduced factor VIII activity, while the mother and son have normal levels. The family asks whether the daughter's children will be affected and whether the son can pass the condition on. The clinic has no genetic testing available and must reason from the pedigree and the pattern of inheritance.
1. Propose the most likely mode of inheritance and justify it from the pattern in the family.
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The pattern fits X-linked recessive inheritance of haemophilia A (factor VIII deficiency). The father, who has one X chromosome, is affected; his daughter receives his affected X and, with a normal X from her mother, is a carrier - which explains her reduced factor VIII and bleeding after extraction. The son receives his father's Y, not the X, so he is unaffected and does not carry the allele. The mother's normal levels are consistent with her being a non-carrier, though a carrier mother could also give this pattern. The reasoning rests on the sex-linked pattern, not on recall of the disease name alone.
2. What is the probability that the daughter's sons would be affected, and what assumptions underpin your answer?
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If the daughter is a carrier (one affected X, one normal X), each son has a 1 in 2 chance of inheriting the affected X and being affected; each daughter has a 1 in 2 chance of being a carrier. This assumes the father is the source of her affected X, that she is a carrier rather than affected, and that no new mutation or other cause is involved. Because genetic testing is unavailable, the estimate is a probability, and counselling should present it as such, with the option of referral for testing if it becomes available.
3. The son asks whether his children can inherit the condition. Answer him and explain the reasoning.
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Under X-linked recessive inheritance, the son inherited his father's Y chromosome and a normal X from his mother, so he does not carry the haemophilia allele. His children cannot inherit the condition from him on this basis. The caveat is that the conclusion depends on the assumed inheritance pattern and on the mother's status; if she were a carrier, the son could still be unaffected but the family risk would differ. The answer should state the assumption explicitly rather than giving a bare 'no'.