Chromosome instability syndromes

Diseases associated with impaired repair, more commonly called chromosomal instability syndromes or chromosome fragility syndromes share some common features. These are autosomal recessive syndromes associated with increased sensitivity to UV radiation and other mutagens. They are often associated with hyper or hypopigmentation, small stature and with immune defect. The high sensitivity of patients to mutagens is associated with an increased level of chromatid and chromosome breaks and chromosome exchanges in their cells. In some diseases, these changes are specific (e.g. increased level of sister chromatid exchanges and exchanges between homologous chromosomes in Bloom syndrome, specific breaks on chromosomes 7 and 14 in ataxia telangiectasia and Nijmegen breakage syndrome). The level of acquired chromosomal aberrations is increased spontaneously, or patients' cells are hypersensitive to the in vitro induction of mutagen aberrations. Because it is a repair or replication disorder, patients have a multiple increased risk of developing cancer.

Cytogenetic effect (increased chromosomal instability) and increased risk of tumors are also shown by syndromes associated with premature aging such as Werner's syndrome (cataracts, subcutaneous calcification, skin changes, premature graying, premature arteriosclerosis - WRN gene - DNA helicase/exonuclease RECQL2) and Cockayne syndrome (dwarfism, mental retardation, deafness, premature senility - CSA (ERCC8), CSB (ERCC6) genes), in patients expressing also symptoms of xeroderma pigmentosum (XP/CS) genes XPB (ERCC3), XPD (ERCC2), XPG (ERCC5).

Related Articles

 * Chromosomal Abnormalities
 * Mutation and Mutagenesis
 * DNA Repair
 * Ataxia teleangiectasia
 * Bloom syndrome
 * Fanconi anemia