ceroid-lipofuscinosis, neuronal 5
The CLN5 gene provides instructions for making a protein whose function is not well understood. Cells produce a CLN5 protein that is inactive and contains extra protein segments. This inactive protein is called a preprotein. For the CLN5 preprotein to become active, the additional segments must be removed, followed by additional processing steps. The active CLN5 protein is then transported to cell compartments called lysosomes, which digest and recycle different types of molecules. Research suggests that the CLN5 protein may play a role in the process by which lysosomes break down or recycle damaged or unneeded proteins within cells.
At least 35 mutations in the CLN5 gene have been found to cause CLN5 disease. This condition impairs mental and motor development causing difficulty with walking and intellectual function. In addition, affected children often develop recurrent seizures (epilepsy) and vision loss. Signs and symptoms of CLN5 disease typically appear around age 5 but can begin in adolescence or adulthood.
Most of the mutations that cause CLN5 disease make changes in the CLN5 protein that interfere with the processing of the preprotein or alter the structure of the protein. The resulting proteins cannot be transported to the lysosomes. Other mutations lead to production of abnormal proteins that are quickly broken down. One such mutation, known as Finmajor, is responsible for almost all cases of CLN5 disease in people of Finnish descent. The Finmajor mutation replaces the protein building block (amino acid) tyrosine with a signal to stop protein production prematurely (written as Tyr392Ter or Y392X).
A lack of functional CLN5 protein within lysosomes probably impairs the breakdown of certain proteins, which then likely accumulate in cells throughout the body. While these accumulations can damage any cells, nerve cells appear to be particularly vulnerable. Widespread loss of nerve cells in CLN5 disease leads to severe signs and symptoms and early death.
In the cases in which CLN5 disease develops in adolescence or adulthood, it is thought that the CLN5 gene mutations lead to a CLN5 protein with reduced function that is broken down earlier than normal. Because the altered CLN5 protein can function for a small amount of time, some damaged or unneeded proteins may be broken down in lysosomes. Since it takes longer for these substances to accumulate and cause nerve cell death, the signs and symptoms of CLN5 disease in these individuals occur later in life.
- ceroid-lipofuscinosis neuronal protein 5