Chromosome fragility in Fanconi anemia patients: diagnostic implications and clinical impact

Fanconi anemia (FA) is a rare syndrome characterized by bone marrow failure, malformations, and cancer predisposition. Chromosome fragility induced by DNA interstrand crosslink (ICL)-inducing drugs is the gold standard diagnostic test for FA. We present data from 198 chromosome fragility tests and propose a new chromosome fragility index that provides a cut-off diagnostic level to unambiguously distinguish FA patients. Our data reveal a correlation between malformations and sensitivity to ICLs suggesting that genome instability during embryo development may be related to FA malformations. Finally, chromosome fragility does not correlate with the age of onset of the blood disease, indicating that chromosome fragility has no prognostic value in FA. (By Professor Jordi Surrallés, http://jmg.bmj.com/content/48/4/242 )