Fanconi Anemia Erica Antell

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Fanconi Anemia Erica Antell
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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.

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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.
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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.

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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.

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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

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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.

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Protein Structure
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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
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Conserved Domain for FA
gi 9837097 116 REELLIALFFFSLMGLLSSYLTQRDTAEHLKAVDI
CAEVLTCLERRKVSWLVLFQLTEKDAKLG 179 gi
12643546 1253 REELLVFLFFFSLMGLLSSHLTSNSTTDLPKAFHVC
AAILECLEKRKISWLALFQLTESDLRLG 1316
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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.