Fanconi anemia is an inherited genetic disorder characterized by bone marrow failure, congenital abnormalities and increased risk of cancer. Common signs and symptoms of Fanconi anemia include lower than normal levels of white blood cells, red blood cells and platelet, leading to frequent infections, fatigue due to inadequate oxygen and inability to clot normally. Some may have physical abnormalities and developmental problems, involving hypopigmentation, loss of hearing, malformed limbs or organs. Some may have maldeveloped, immature blood cells that can give rise to serious conditions such as leukemia (cancer in the blood cells). Fanconi anemia is caused by a genetic defect of the proteins involved in the Fanconi anemia (FA) pathway. The FA pathway is essential for repairing damaged DNA, particularly covalent cross-links, which can block DNA replication and transcription. Fanconi anemia group C is a form commonly found among people of Ashkenazi Jewish descent, and it is caused by mutations in the FANCC (Fanconi Anemia Complementation group C) gene. There are more than 50 mutations identified in the FANCC to date. Mutations in the FANCC gene that cause Fanconi anemia can affect the function of the protein. Two specific mutations of interest, IVS4+4A>T and 322delG, can lead to absent or reduced protein function. This disrupts the FA pathway, resulting in accumulation of errors in damaged DNA due to the inability to repair properly. As a consequence, DNA replication is blocked, leading to abnormal cell death or uncontrolled cell growth, giving rise to the characteristics of Fanconi anemia. References: Alter BP, Kupfer G (2002) [Updated 2013 Feb 7]. Fanconi Anemia. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Jose CP, Ferreira MD, Schreiber-Agus N, Carter SM, Klugman S, MDa, Gregg AR, Gross SJ (2014). Carrier testing for Ashkenazi Jewish disorders in the prenatal setting: navigating the genetic maze. American Journal of Obstetrics and Gynecology. 211(3): 197-204. de Vries Y, Lwiwski N, Levitus M, et al. (2012). A Dutch Fanconi Anemia FANCC Founder Mutation in Canadian Manitoba Mennonites. Anemia, vol. 2012, Article ID 865170. Whitney MA, Saito H, Jakobs PM, Gibson RA, Moses RE, Grompe M (1993). A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews. Nat Genet. 4(2): 202-5.