C9orf72

The C9orf72 gene provides instructions for making a protein that is found in many tissues but whose function is unknown. Three different versions (isoforms) of the C9orf72 protein are produced from the C9orf72 gene. These isoforms are likely found in different tissues, but their purpose is unclear. The C9orf72 protein is produced in many regions of the brain. Within nerve cells (neurons), the protein is found in the fluid surrounding the nucleus (the cytoplasm). Additionally, the C9orf72 protein seems to be located in specialized structures called presynaptic terminals, found at the tips of neurons.

amyotrophic lateral sclerosis - caused by mutations in the C9orf72 gene

Mutations in the C9orf72 gene have been found to cause amyotrophic lateral sclerosis (ALS), a condition characterized by progressive movement problems and muscle wasting. The normal C9orf72 gene contains a region where a series of six DNA building blocks (nucleotides) occurs once or can be repeated multiple times. This stretch of nucleotides consists of four guanines and two cytosines (written as GGGGCC). When this series of nucleotides is repeated too many times, it can cause ALS. This type of mutation is called a hexanucleotide repeat expansion. Although it is not clear exactly how many hexanucleotide repeats are needed to cause disease, researchers believe that having more than about 30 repeats can lead to ALS. The hexanucleotide repeat expansion in the C9orf72 gene appears to reduce the amount of C9orf72 protein that is produced. The protein that is produced may be altered and may interfere with cell function. It is unclear how decreased or altered C9orf72 protein causes the signs and symptoms of ALS.

Some people with ALS caused by C9orf72 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 C9orf72 gene mutations develop FTD and others do not. Individuals who develop both conditions are diagnosed as having ALS-FTD.