The CLN3 gene provides instructions for making a protein called battenin. This protein is primarily located in the membranes of lysosomes and endosomes, which are compartments within the cell that digest and recycle materials. The protein can also be found in the membrane that surrounds the cell and in the membrane of the Golgi apparatus, which is a cell structure that modifies newly produced enzymes and other proteins. The function of battenin in these cellular structures is unclear.
Studies have associated battenin with many cellular processes, including recycling of worn-out cell parts and unneeded proteins (autophagy), maintenance of the relative acidity (pH) of lysosomes, the movement of molecules from the cell surface into the cell (endocytosis), transportation (trafficking) of proteins to where they are needed in the cell, self-destruction of cells (apoptosis), cell growth and division (proliferation), and maintenance of the body's water balance (osmoregulation). It is uncertain whether any of these varied functions is the primary role of battenin, or if they represent downstream effects.
More than 65 mutations in the CLN3 gene have been found to cause CLN3 disease. CLN3 disease is an inherited disorder that primarily affects the nervous system. Children with this condition develop worsening vision impairment, intellectual disability, movement problems, speech difficulties, and seizures.
One CLN3 gene mutation, found in more than 90 percent of cases, deletes about 1,000 DNA building blocks (base pairs) in the gene. This mutation, which is usually called the 1 kilobase (kb) deletion, removes a piece of the CLN3 gene and leads to the production of an abnormally short protein that is probably broken down quickly. As a result, there is a severe reduction in the amount of functional battenin in cells. Other mutations also reduce the amount or impair the function of battenin. It is not known how the loss of this protein causes the signs and symptoms of CLN3 disease.
CLN3 disease is characterized by the accumulation of proteins and other substances in lysosomes. These accumulations occur in cells throughout the body; however, nerve cells seem to be particularly vulnerable to their effects. The accumulations can cause cell damage leading to cell death. The progressive death of nerve cells in the brain and other tissues leads to the neurological signs and symptoms of CLN3 disease. Additionally, it is thought that cardiac cell damage and death due to lysosomal accumulations contribute to the heart problems in people with CLN3 disease. However, it is unclear how mutations in the CLN3 gene are involved in the buildup of substances in lysosomes.
- ceroid-lipofuscinosis, neuronal 3