1 Fanconi Anemia Erica Antell
2 What 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.
3 Clinical 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.
4 Diagnosis and Treatment
Patients are usually smaller than average. Blood tests may show a low WBC, RBC, and platelet count. Fatigue. Frequent infections. Frequent nosebleeds Easy 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.
5 Mutation (Type A FA) Symbol: FANCA Chromosome: 16 Location: 16q24.3
Gene Type: protein coding When this mutation occurs, the incorrect protein (FANCA) is transcribed as opposed to the wild type, resulting in characteristics of the fanconi anemia phenotype.
6 Gene Structure By 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 37 23 bp deletion at the 5 prime end at exon 41 GCAG insertion at the 3 prime end at exon 41
7 Protein 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.
9 DNA Sequence (FANCA gene)
894 base pairs atgtccgact cgtgggtccc gaactccgcc tcgggccagg acccaggggg ccgccggagg gcctgggccg agctgctggc gggaagggtc aagagggaaa aatataatcc tgaaagggca cagaaattaa aggaatcagc tgtgcgcctc ctgcgaagcc atcaggacct gaatgccctt ttgcttgagg tagaaggtcc actgtgtaaa aaattgtctc tcagcaaagt gattgactgt gacagttctg aggcctatgc taatcattct agttcattta taggctctgc tttgcaggat caagcctcaa ggctgggggt tcccgtgggt attctctcag ccgggatggt tgcctctagc gtgggacaga tctgcacggc tccagcggag accagtcacc ctgtgctgct gactgtggag cagagaaaga agctgtcttc cctgttagag tttgctcagt atttattggc acacagtata ttctcccgtc tttccttctg tcaagaatta tggaaaatac agagttcttt gttgcttgaa gcggtgtggc atcttcacgt acaaggcatt gtgagcctgc aagagctgct ggaaagccat cccgacatgc atgctgtggg atcgtggctc ttcaggaatc tgtgctgcct ttgtgaacag atggaagcat cctgccagca tgctgacgtc gccagggcca tgctttctga ttttgttcaa atgtttgttt tgaggggatt tcagaaaaac tcagatctga gaagaactgt ggagcctgaa aaaatgccgc aggtcacggt tgatgtactg cagagaatgc tgatttttgc acttgacgct ttggctgctg gagtacagga ggagtcctcc actcacaaga tcgtgaggtg ctga
10 Conserved Domain for FA
gi REELLIALFFFSLMGLLSSYLTQRDTAEHLKAVDICAEVLTCLERRKVSWLVLFQLTEKDAKLG gi REELLVFLFFFSLMGLLSSHLTSNSTTDLPKAFHVCAAILECLEKRKISWLALFQLTESDLRLG 1316
11 References Thompson, 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.