2.1 Amyotrophic Lateral Sclerosis

At least 85 mutations in the FUS gene have been found to cause amyotrophic lateral sclerosis (ALS), a condition characterized by progressive muscle weakness, a loss of muscle mass, and an inability to control movement. Most of these mutations change single protein building blocks in the FUS protein and often affect the region of the protein involved in DNA binding and mRNA processing. These mutations may interfere with the transport of mRNA out of the nucleus of cells. As a result, FUS protein and mRNA are trapped within cells and likely form clumps (aggregates), which have been found in nerve cells that control muscle movement (motor neurons) in some people with ALS. It is unclear if protein aggregates cause the nerve cell death that leads to ALS. People with ALS caused by mutations in the FUS gene tend to develop the disease at a younger age and have a decreased life expectancy compared with individuals who have sporadic ALS or ALS caused by mutations in other genes.

Rarely, people with ALS caused by FUS gene mutations also develop a condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. It is unclear why some people with FUS gene mutations develop FTD and others do not. Individuals who develop both conditions are diagnosed as having ALS-FTD.

2.2 Ewing Sarcoma

2.3 Cancers

Specific mutations involving the FUS gene are involved in several types of cancer. The mutations that cause these tumors are acquired during a person's lifetime and are present only in the tumor cells. This type of genetic change, called a somatic mutation, is not inherited. Most commonly, mutations in this gene are found in tumors called soft tissue sarcomas, which develop in bones or in soft tissues such as nerves or cartilage. FUS gene mutations have also been found in myxoid liposarcomas, which occur in fatty tissues of the body, and in cancer of the blood-forming cells in the bone marrow called acute myeloid leukemia (AML). The genetic changes associated with these cancers are rearrangements (translocations) of genetic material between chromosome 16 (where the FUS gene is located) and other chromosomes. These translocations break chromosome 16 in the middle of the FUS gene and fuse it with another gene on a different chromosome, creating a fusion gene. Fusion genes usually have partial function of both genes involved. The FUS gene promotes DNA transcription and protein production, which helps promote cell growth; this gene might fuse with another gene that could allow cell growth to continue at a rapid pace. When cell growth is left uncontrolled, cancer can develop.