The first person in a family to exhibit Leber hereditary optic neuropathy (LHON) was II-3 in the pedigree shown below, and all of her children also exhibited the disease. Provide two possible explanations as to why II-3's mother (I-1) did not exhibit symptoms of LHON.

Verified step by step guidance

1. Identify that Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder, which means it is passed through the maternal line.
2. Observe that individual II-3 is affected and all her children (III-1, III-2, III-3) are also affected, indicating maternal inheritance.
3. Consider that I-1, the mother of II-3, might not exhibit symptoms due to heteroplasmy, where a mixture of normal and mutated mitochondria exists, and the proportion of mutated mitochondria is not sufficient to cause symptoms.
4. Another possibility is that I-1 has a lower penetrance of the disease, meaning she carries the mutation but does not express the symptoms due to other genetic or environmental factors.
5. Conclude that the absence of symptoms in I-1 does not preclude her from being a carrier of the mitochondrial mutation responsible for LHON.

Key Concepts

Leber Hereditary Optic Neuropathy (LHON)

LHON is a mitochondrial genetic disorder that primarily affects the optic nerve, leading to vision loss. It is caused by mutations in mitochondrial DNA, which is inherited maternally. The disease typically manifests in young adults, and while it can affect both genders, males are more frequently affected. Understanding LHON's inheritance pattern is crucial for analyzing family pedigrees.

Mitochondrial Inheritance

Mitochondrial inheritance refers to the transmission of genetic traits through mitochondrial DNA, which is passed from mothers to all their offspring. This type of inheritance explains why II-3's children exhibit LHON, as they inherit the affected mitochondrial DNA from their mother. However, it also clarifies why II-3's mother (I-1) may not show symptoms, as not all individuals with mitochondrial mutations express the disease due to factors like variable expressivity.

Variable Expressivity

Variable expressivity is a phenomenon where individuals with the same genetic mutation exhibit different degrees of severity or even different symptoms of a disease. In the context of LHON, I-1 may carry the mutation but not express the disease due to factors such as environmental influences, other genetic factors, or the specific nature of the mutation. This concept is essential for understanding why some family members may be asymptomatic despite carrying the same genetic risk.