C9orf72

About C9orf72

C9orf72, an open reading frame on chromosome 9p21.2, encodes a protein involved in membrane trafficking and autophagy. In 2011 two research groups independently identified a large expansion of a GGGGCC hexanucleotide repeat in a non coding region of the gene as the most common genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia, unifying two conditions that were already known to overlap clinically and pathologically. The expansion is thought to cause disease through several mechanisms, including reduced C9orf72 protein, toxic RNA foci, and dipeptide repeat proteins produced by unconventional translation of the repeat. Inheritance is autosomal dominant with incomplete penetrance, and the expansion is especially frequent in people of Northern European ancestry, including in Finland. It is also found in some people diagnosed with ALS or frontotemporal dementia who have no family history.