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Fanconi Anemia
Erica Antell
What is Fanconi Anemia?
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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.
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.
Diagnosis and Treatment
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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.
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Hematopoietic (blood-stimulating) growth factors are used to stimulate
WBC production.
Androgens.
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Male hormones often stimulate the production of RBCs and platelets.
Mutation (Type A FA)
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Symbol: FANCA
Chromosome: 16
 Location: 16q24.3
Gene Type: protein coding
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When this mutation occurs, the incorrect protein (FANCA) is transcribed
as
opposed to the wild type, resulting in characteristics of the fanconi
anemia
phenotype.
Gene Structure
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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
Protein
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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.
Protein Structure
DNA Sequence (FANCA gene)
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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
Conserved Domain for FA
gi 9837097 116 REELLIALFFFSLMGLLSSYLTQRDTAEHLKAVDICAEVLTCLERRKVSWLVLFQLTEKDAKLG 179
12643546 1253 REELLVFLFFFSLMGLLSSHLTSNSTTDLPKAFHVCAAILECLEKRKISWLALFQLTESDLRLG 1316
gi
References
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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.