SNP Shot: Genomic Insights

CLN11 disease is a neurological disorder that typically manifests in adolescence or early adulthood. Its primary characteristics include recurrent seizures (epilepsy), progressive vision loss, balance and coordination difficulties (cerebellar ataxia), and cognitive decline.

The seizures associated with CLN11 disease often involve loss of consciousness, muscle rigidity, and generalized tonic-clonic convulsions.

Vision loss progresses gradually due to retinitis pigmentosa, a condition resulting from the degeneration of the retina's light-sensitive layer. Additionally, individuals with CLN11 disease may experience cataracts (clouding of the eye's lens) and nystagmus (involuntary, rapid eye movements).

Other symptoms can include myoclonus (muscle twitches), gait disturbance (walking problems and falls), and dysarthria (impaired speech). Over time, individuals may develop short-term memory loss and impaired executive function, impacting their ability to plan and solve problems. Irritability, impulsivity, and visual hallucinations involving people or animals can also occur.

CLN11 disease belongs to a group of neurological disorders called neuronal ceroid lipofuscinoses (NCLs). These disorders commonly lead to progressive vision, movement, and cognitive impairment. The different NCL subtypes are differentiated by their specific genetic cause and designated with a "CLN" label followed by a number indicating the subtype.

Inheritance:

CLN11 disease follows an autosomal recessive inheritance pattern, meaning that both copies of the GRN gene in each cell must have mutations for the disease to manifest. These mutations prevent the production of functional progranulin protein. The parents of individuals with CLN11 disease each carry one copy of the mutated GRN gene and typically produce about half the normal amount of progranulin. While these carriers usually don't show symptoms of CLN11 disease, they are at risk for developing GRN-related frontotemporal lobar degeneration later in life, a condition causing cognitive decline that typically begins between ages 40 and 60. Interestingly, some individuals with two GRN gene mutations that still allow for some functional progranulin production may also develop GRN-related frontotemporal lobar degeneration.