Overview of FA for the hematology student.

1. FANCONI ANEMIA
PRESENTED BY: MOHAMMADREZA JAVAN
SUPERVISOR: DR.SADEGHIYAN

2. MECHANISM
•Proteins:
•1-BRCA
2-FANC

4. •Complex 1: FCC (11 upto 13 pr)
•Complex 2: FCC+Prs
•Complex3: RMN(MRE11,negmegan, Rab50)
•FANCE L: ubiquitination for FANCD & FANCE I
•Final complex

5. WHAT IS FANCONI ANEMIA?
Heterozygote
Homozygote
Fanconi anemia:
an autosomal recessive disorder resulting from a heterogeneous molecular
1 in 350,000 live birth in North America.
Fanconi anemia is one of the inherited anemias that causes bone marrow failure.r.
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.
Increase : AML, MDS, CML-L (1500)
Patients are very likely to develop squamous cell carcinomas.

6. CLINICAL MANIFESTATIONS
1- physical abnormalities: 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.
2- bone marrow failure: Progressive bone marrow failure with pancytopenia typically presents
in the first decade, often initially with thrombocytopenia or leukopenia.
3- increased risk of malignancy

7. DIAGNOSIS
CBC:
Pancytopenia, macrocytic (although it can be normocytic) blood cells
MCV(more than 120), thrombocytopenia, anemia, neutropenia
Blood banking :
Erythrocytes often show increased levels of Hemoglobin F and the “i” antigen
Karyotyping :
Karyotyping of FA cells shows increased spontaneous
chromosomal breakage, gaps, rearrangements, exchanges ,
and duplications.

8. DIAGNOSIS
DEB: (Gold standard)
exposing blood lymphocytes or skin fibroblasts to crosslinking agents such as
mitomycin C, diepoxy butane, or cisplatin that amplify chromosomal breakage.
Molecular techniques:
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

9. DIAGNOSIS
Bone marrow biopsy:
Hypoplasia
Immunoblotting:
monoubiquitin FAncD2

10. DIAGNOSIS
Flowcytometry :
Check Cell cycle out
Prolonged G2 phase
Elevated apoptosis

11. TREATMENT
Growth factors
Bone marrow transplant
Anti-biotics
Blood transfusions
Androgen drugs such as Oxymethanol

12. REFERENCES
1-DACIE AND LEWIS PRACTICAL HAEMATOLOGY
2-mackenzy
3-Richard A. McPherson MD MSc, Matthew R. Pincus MD PhD-Henry’s Clinical Diagnosis and
Management by Laboratory Methods, 23e-Elsevier (2016)
4- Thompson, E, Dragovic, RL, Campbell, IG. “FANCA: Fanconi Anemia.” PubMed. April 29, 2005.
5-Ferrer, M, Rodriguez, JA, Spierings, Ea, Kruyt, FA. “Identification of Multiple Export Sequences Related
to Fanconi Anemia.” PubMed. March 24, 2005.
6--Alberts, Johnson, Lewis, Raff, Roberts, Walter. “Inherited Syndroms With Defects in DNA Repair.”
Molecular Biology of the Cell. October 15, 2004.

13. REFERENCES
7-Lodish, Harvey, Berk, Arnold. “Peroxisomal Protein Import is Defective in Some Genetic Disorders.
Molecular Cell Biology. July 23, 2003.
8-http://www.nlm.nih.gov/medlineplus/ency/article/000334.htm - medicine plus
9-http://www.fanconi.org/aboutfa/FA.htm - Fanconi Research Fund
10-theyorf.blogspot.com/2007/10/fanconi-anaemia-...
11-http://www.nature.com/nm/journal/v8/n6/full/nm0602-555.html - nature medicine