A 25-year-old man experiences severe intolerance to certain medications. On 2 occasions, his reactions to various drugs have necessitated hospital admission. His family pedigree with respect to this condition is shown below, with the red arrow indicating his position within the family.
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Assuming that the genetic condition demonstrates complete penetrance and is rare in the general population, which of the following inheritance patterns is most likely?
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The pedigree shows that only males are affected by the drug intolerance. Specifically, male offspring of unaffected parents are affected. There is no evidence of male-to-male transmission. This pattern is most consistent with X-linked recessive inheritance from an asymptomatic carrier female in the first generation. In X-linked recessive inheritance:
G6PD deficiency, which causes acute hemolytic anemia on exposure to oxidant drugs, follows an X-linked recessive pattern of inheritance.
(Choice A) With autosomal dominant inheritance, affected individuals have at least 1 parent that is also affected.
(Choice B) In autosomal recessive inheritance, both parents must at least be carriers (heterozygous) for the mutation in order to produce affected offspring. However, the father of the marked individual comes from outside the family and would be unlikely to carry the mutation (the question states the mutation is rare in the general population).
(Choice C) In X-linked dominant inheritance, affected individuals have at least 1 parent (of either sex) that is also affected. An affected male will always produce affected daughters, but none of his sons will be affected.
(Choice E) Conditions with mitochondrial inheritance are transmitted only by females. All of an affected female’s offspring are likely to show signs of the disease.
Educational objective:
In X-linked recessive inheritance 1) affected males will always produce unaffected sons and carrier daughters, and 2) carrier females have a 50% chance of producing affected sons and carrier daughters. G6PD deficiency follows this inheritance pattern and causes acute hemolytic anemia in response to oxidant drugs.