Mitochondrial inheritance · USMLE Step 1

Which of the following is a potential challenge when diagnosing mitochondrial diseases using family history alone?

  1. mtDNA always recombines, making lineage tracing hard
  2. Variable heteroplasmy and penetrance can mask maternal transmission
  3. Both parents transmit mtDNA in equal amounts
  4. mtDNA is identical across all individuals
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Correct answer: Variable heteroplasmy and penetrance can mask maternal transmission

Because heteroplasmy can vary between individuals and tissues, and disease expression depends on mutant load, an affected mother might appear asymptomatic — obscuring maternal transmission when relying solely on pedigree.

Difficulty: Medium Question 15 of 19

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