FANCA gene

Hundreds of variants (also called mutations) in the FANCA gene have been found to cause Fanconi anemia, a disorder characterized by a decrease in bone marrow function, an increased cancer risk, and physical differences. Variants in the FANCA gene are responsible for 60 to 70 percent of all cases of Fanconi anemia. These variants change single DNA building blocks (nucleotides) or insert or delete pieces of DNA in the FANCA gene. Some of these variants produce a FANCA protein that can partially function; other variants prevent the production of any FANCA protein.

Variants in the FANCA gene lead to a nonfunctional FA core complex, which disrupts the entire FA pathway. As a result, DNA damage is not repaired efficiently and ICLs build up over time. The ICLs impair DNA replication, which leads to abnormal cell death due to an inability to make new DNA molecules or uncontrolled cell growth due to a lack of DNA repair. 

Cells that divide quickly, such as bone marrow cells and cells of the developing fetus, are particularly sensitive to problems with DNA replication. The death of these cells results in the decrease in blood cells and the physical differences characteristic of Fanconi anemia. When the buildup of errors in DNA leads to uncontrolled cell growth, affected individuals can develop certain cancers.