In mitochondrial diseases, what term explains why there is variable clinical expression among family members?

In mitochondrial diseases, what term explains why there is variable clinical expression among family members?

• A. Heteroplasmy
• B. Penetrance
• C. Expressivity
• D. Mosaicism

Answer: (A)

Heteroplasmy explains why clinical expression varies among family members. In each cell, many mitochondria carry multiple copies of mitochondrial DNA, and a mutation may be present in only a fraction of those copies. The proportion of mutant to normal mtDNA—heteroplasmy—differs between individuals and even between tissues within the same person. Disease tends to manifest only when the mutant load in a tissue crosses a certain threshold, so some people with the mutation are asymptomatic or have milder disease, while others have more severe symptoms. Because mitochondrial DNA is inherited from the mother, the amount of mutant mtDNA transmitted to each child can vary, producing different phenotypes in siblings. This mechanism best accounts for the observed variability.

Heteroplasmy explains why clinical expression varies among family members. In each cell, many mitochondria carry multiple copies of mitochondrial DNA, and a mutation may be present in only a fraction of those copies. The proportion of mutant to normal mtDNA—heteroplasmy—differs between individuals and even between tissues within the same person. Disease tends to manifest only when the mutant load in a tissue crosses a certain threshold, so some people with the mutation are asymptomatic or have milder disease, while others have more severe symptoms. Because mitochondrial DNA is inherited from the mother, the amount of mutant mtDNA transmitted to each child can vary, producing different phenotypes in siblings. This mechanism best accounts for the observed variability.