Changes of chromatin condensation in one patient with ataxia telangiectasia disorder: A structural study

Differential scanning calorimetry and quantitative fluorescence microscopy have been employed to characterize the structure and organization of in sit u chromatin in lymphoblastoid cells obtained from one ataxia telangiectasia (A-T) patient and one healthy family member. The proven capability of thes e biophysical techniques to measure changes of chromatin condensation direc tly inside the cells makes them very powerful in studying the eventual stru ctural changes associated with the appearance of a pleiotropic genetic diso rder such as ataxia telangiectasia. A-T syndrome is genetically heterogeneo us and can be induced by different mutations of a single gene. The aim of t his work is to determine whether the genetic mutation exhibited by the A-T patient of this study may be associated with modifications of chromatin str ucture and organization. Both the calorimetric and the fluorescence microsc opy results acquired on cells From the A-T patient show that the structure and distribution of nuclear chromatin in situ change considerably with resp ect to the control. A significant decondensation of the nuclear chromatin i s in fact associated with the appearance of the A-T disorder in the A-T pat ient under analysis, together with a rearrangement of the chromatin domains inside the nucleus. (C) 1999 Wiley-Liss, Inc.