SNP Shot: Genomic Insights

Leber hereditary optic neuropathy (LHON) is an inherited condition causing vision loss. Typically, the condition manifests during a person's teenage or early adult years (twenties), though rare instances can occur in early childhood or later in life. Interestingly, males are significantly more likely to be affected than females, for reasons currently not understood.

The initial signs of LHON usually involve blurred and clouded vision. These visual disturbances may appear in one eye first, or simultaneously in both. If one eye is affected initially, the other eye generally experiences similar symptoms within weeks or months. Over time, vision deteriorates in both eyes, resulting in a substantial decrease in visual acuity (sharpness) and color perception. The condition primarily impacts central vision, which is essential for tasks requiring detail, such as reading, driving, and recognizing faces. This vision loss stems from the death of cells within the optic nerve, which transmits visual information from the eyes to the brain. While a small percentage of individuals experience gradual improvement in central vision, most experience profound and irreversible vision loss.

Typically, vision loss is the sole symptom of LHON. However, some families exhibit additional signs and symptoms, referred to as "LHON plus." These additional features can include movement disorders, tremors, and irregularities in the electrical signals that regulate the heartbeat (cardiac conduction defects). Some individuals develop symptoms resembling multiple sclerosis, a chronic condition characterized by muscle weakness, impaired coordination, numbness, and various other health issues.

Inheritance:

LHON follows a mitochondrial inheritance pattern, also known as maternal inheritance. This pattern applies to genes located in mitochondrial DNA (mtDNA). Since mitochondria are passed to the developing embryo through the egg cell, but not the sperm cell, children can only inherit disorders caused by mtDNA mutations from their mother. These disorders can appear in every generation and affect both sexes. However, fathers cannot pass on mtDNA-related traits to their children.

Frequently, individuals who develop LHON have no prior family history of the condition. Because an individual can carry an mtDNA mutation without showing any signs or symptoms, predicting which family members carrying the mutation will ultimately develop vision loss or other LHON-related problems is challenging. Crucially, all females carrying an mtDNA mutation, even those without any symptoms, will pass the genetic change on to their offspring.