Chromosomal instability syndromes

Diseases associated with impaired DNA repair, more commonly called chromosomal instability syndromes or syndromes associated with increased fragility of chromosomes show 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, short stature and an 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 chromosome 7 and 14 in ataxia telangiectasia and Nijmegen breakage syndrome). The level of acquired chromosomal aberrations is increased spontaneously, or the patient’s cells are more sensitive to the in vitro induction of aberrations by mutagens. Because this is a repair or replication disorder, patients have a multifold increased risk of developing cancer.

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

Related articles

 * Chromosomal abnormality
 * Mutation and Mutagenesis
 * DNA repair
 * Ataxia telangiectasia
 * Bloom syndrome
 * Fanconi anemia