Fanconi anemia (FA) is a rare genetic disease characterized by chromosome 
instability, progressive pancytopenia and cancer susceptibility. Telomeres are 
intimately related to chromosome stability and play an important role in 
organismal viability at the hematological level. Since previous works suggested 
an accelerated shortening of telomeres in FA, we have studied several markers of 
telomere integrity and function in FA patients and age-matched controls to get 
insights into the mechanisms and consequences of telomere erosion in FA. A 
higher frequency of extra-chromosomic TTAGGG signals and of chromosome ends with 
undetectable TTAGGG repeats was observed in FA cells by fluorescence in situ 
hybridization (FISH), suggesting intensive breakage at telomeric sequences. This 
was proven by measuring the frequency of excess of telomeric signals per cell, 
which was 2.8-fold higher in FA. Consistent with previous reports, quantitative 
FISH analysis showed an accelerated telomere shortening of 0.68 kb in FA, which 
occurred concurrently in both chromosome arms in a similar magnitude. Our data 
therefore suggest that the telomere erosion in FA is caused by a higher rate of 
breakage at TTAGGG sequences in vivo in differentiated cells, in addition to 
mere replicative shortening during lymphocyte proliferation. Consistent with 
impaired telomeres in FA patients, we observed a >10-fold increase in chromosome 
end fusions in FA compared to normal controls. This observation was independent 
of TRF2, a telomere binding factor that protects human telomeres from end 
fusions, since immunohistochemistry studies in FA cell lines and corrected 
counterparts by retrovirus-mediated transfer of FANCA and FANCD2 cDNA showed 
that a functional FA pathway is not required for telomere binding of TRF2.