TSC1

The TSC1 gene provides instructions for producing a protein called hamartin. While the function of hamartin is not fully understood, it is known that within cells this protein interacts with another protein called tuberin. These two proteins likely function together as a protein complex that helps regulate cell growth and size. Proteins that normally prevent cells from growing and dividing too fast or in an uncontrolled way are known as tumor suppressors.

tuberous sclerosis - caused by mutations in the TSC1 gene

More than 100 inherited mutations in the TSC1 gene have been identified in individuals with tuberous sclerosis. Most of these mutations involve either small deletions or insertions of DNA in the TSC1 gene. Some mutations create a premature stop signal in the instructions for making hamartin. These alterations produce an abnormal version of hamartin that cannot form a complex with tuberin. Loss of this protein complex causes an overgrowth of cells that grow too large and/or divide too often, resulting in noncancerous tumors in many tissues of the body.

bladder cancer - associated with the TSC1 gene

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic TSC1 mutations in bladder cells have been identified in some cases of bladder cancer. In some of these cells, one copy of the TSC1 gene is missing because the region of chromosome 9 containing the gene has been deleted; the other copy of the gene has a mutation that interferes with its function. As a result, little or no hamartin is produced. A loss of hamartin in bladder cells may allow these cells to grow and divide without control, leading to the formation of a cancerous tumor.

It is unclear why inherited TSC1 mutations lead to the noncancerous growths characteristic of tuberous sclerosis, while somatic mutations in this gene are associated with the development of cancerous tumors.

other disorders - caused by mutations in the TSC1 gene

Inherited mutations in the TSC1 gene may also cause a disorder called lymphangioleiomyomatosis, although mutations in a related gene called TSC2 appear to be responsible for most cases of this disorder. This destructive lung disease is caused by the abnormal overgrowth of smooth muscle tissue in the lungs. Symptoms include coughing, shortness of breath, chest pain, and lung collapse. This condition can occur alone or in combination with tuberous sclerosis.

Hereditary mutations in TSC1 can also cause a disorder known as focal cortical dysplasia of Taylor balloon cell type. This disorder results from malformations of the cerebrum, the frontal part of the brain that is responsible for thinking and learning. Focal cortical dysplasia causes severe seizures (epilepsy) in affected individuals.