2.1 Fanconi Anemia

At least 50 mutations in the FANCC gene have been found to cause Fanconi anemia, a disorder characterized by a decrease in bone marrow function, an increased cancer risk, and physical abnormalities. Mutations in the FANCC gene are responsible for about 15 percent of all cases of Fanconi anemia. A particular mutation in the FANCC gene has been found in people with Central and Eastern European (Ashkenazi) Jewish background. This mutation (written as 456+4A>T) disrupts the way the gene's instructions are used to make the protein. Individuals with this mutation tend to have more severe signs and symptoms than people who have some of the other mutations in the FANCC gene.

Most mutations in the FANCC gene that cause Fanconi anemia lead to absent or reduced protein function. As a result, the FA core complex cannot function and the entire FA pathway is disrupted. Due to the disrupted pathway, DNA damage is not repaired efficiently and ICLs build up over time. The ICLs stall DNA replication, ultimately resulting in either abnormal cell death due to an inability make new DNA molecules or uncontrolled cell growth due to a lack of DNA repair processes. Cells that divide quickly, such as bone marrow cells and cells of the developing fetus, are particularly affected. The death of these cells results in the decrease in blood cells and the physical abnormalities characteristic of Fanconi anemia. When the buildup of errors in DNA leads to uncontrolled cell growth, affected individuals can develop leukemia or other cancers.