2What is Fanconi Anemia?Fanconi anemia is one of the inherited anemias that causes bone marrow failure.It is a recessive disorder.There are at least 11 different mutations causing fanconi anemia.A*, B, C, D1, D2, E, F, G, I, J, and L.It is considered mainly a blood disease.Many patients eventually develop acute myelogenous leukemia at an early age.Patients are very likely to develop squamous cell carcinomas.
3Clinical Manifestations Fanconi Anemia can be characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. Physical abnormalities of affected individuals include short stature; abnormalities of the thumbs, forearms, skeletal system, eyes, kidneys and urinary tract, ear, heart, gastrointestinal system, oral cavity, and central nervous system; hearing loss; hypogonadism; and developmental delay. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia.
4Diagnosis and Treatment Patients are usually smaller than average.Blood tests may show a low WBC, RBC, and platelet count.Fatigue.Frequent infections.Frequent nosebleedsEasy bruising.Treatments include:Bone marrow transplant.Growth factors.Hematopoietic (blood-stimulating) growth factors are used to stimulate WBC production.Androgens.Male hormones often stimulate the production of RBCs and platelets.
5Mutation (Type A FA) Symbol: FANCA Chromosome: 16 Location: 16q24.3 Gene Type: protein codingWhen this mutation occurs, the incorrect protein (FANCA) is transcribed as opposed to the wild type, resulting in characteristics of the fanconi anemia phenotype.
6Gene StructureBy genomic sequence analysis, it was determined that the FANCA gene contains 43 exons and spans approximately 80 Kb. The exon size ranges from 34 to 188 bp.Three alternative splicing events result in the fanconi anemia mutation. They include:Loss of exon 3723 bp deletion at the 5 prime end at exon 41GCAG insertion at the 3 prime end at exon 41
7Protein The protein responsible for Type A FA is titled FANCA. When one of the three previously mentioned mutations occurs, the FANCA protein is transcribed.The transcription of this protein results in the phenotype described earlier.
10Conserved Domain for FA gi REELLIALFFFSLMGLLSSYLTQRDTAEHLKAVDICAEVLTCLERRKVSWLVLFQLTEKDAKLG gi REELLVFLFFFSLMGLLSSHLTSNSTTDLPKAFHVCAAILECLEKRKISWLALFQLTESDLRLG 1316
11ReferencesThompson, E, Dragovic, RL, Campbell, IG. “FANCA: Fanconi Anemia.” PubMed. April 29, 2005.Ferrer, M, Rodriguez, JA, Spierings, Ea, Kruyt, FA. “Identification of Multiple Export Sequences Related to Fanconi Anemia.” PubMed. March 24, 2005.Alberts, Johnson, Lewis, Raff, Roberts, Walter. “Inherited Syndroms With Defects in DNA Repair.” Molecular Biology of the Cell. October 15, 2004.Lodish, Harvey, Berk, Arnold. “Peroxisomal Protein Import is Defective in Some Genetic Disorders. Molecular Cell Biology. July 23, 2003.National Center For Biotechnology Information.PubMed.OMIM.