SNP Shot: Genomic Insights

Frontotemporal lobar degeneration linked to the GRN gene is a brain disease that worsens over time, impacting behavior, language skills, and movement. Symptoms typically appear between ages 50 and 69, with survival ranging from 7 to 13 years after symptom onset. However, symptoms can start as early as the 30s or as late as the 80s. The specific features of this condition vary widely, even among family members.

Changes in behavior are often the first noticeable signs of GRN-related frontotemporal lobar degeneration. These can include significant shifts in personality, impaired judgment, and a lack of self-awareness. Affected individuals may struggle with social interactions and have difficulty behaving appropriately. They may also become easily distracted, find it hard to finish tasks, and require increasing assistance with personal hygiene and daily routines.

Many individuals with GRN-related frontotemporal lobar degeneration experience increasing difficulties with speech and language (aphasia). They may struggle to speak, have trouble recalling words and names (dysnomia), and find it hard to understand what others are saying. Eventually, they may lose the ability to speak altogether (mutism). This condition also leads to a decline in cognitive abilities (dementia).

Some individuals with GRN-related frontotemporal lobar degeneration also develop movement disorders like parkinsonism and corticobasal syndrome. The signs and symptoms of these disorders can include tremors, muscle stiffness (rigidity), slowed movements (bradykinesia), problems with walking (gait disturbance), involuntary muscle jerks (myoclonus), uncontrolled muscle contractions (dystonia), and difficulty performing purposeful movements (apraxia).

Inheritance:

GRN-related frontotemporal lobar degeneration is inherited through a pattern called incomplete autosomal dominance. This means that having one altered copy of the GRN gene usually results in less severe symptoms than having two copies. People who inherit one mutated GRN gene from either parent (heterozygotes) produce some functional progranulin protein and develop GRN-related frontotemporal lobar degeneration. Generally, individuals who inherit two mutated GRN genes, one from each parent (homozygotes), produce little or no functional progranulin protein. These individuals typically develop CLN11 disease, a condition characterized by movement and neurological issues that begin in adolescence or early adulthood. However, some individuals with two GRN gene mutations that still allow for some progranulin production will develop GRN-related frontotemporal lobar degeneration. In most cases of GRN-related frontotemporal lobar degeneration, affected individuals have a parent or other family members who also have the condition.