[Clinical, biochemical and molecular characterization of rare genetic disorders, related to nucleotide excision...

All living organisms are equipped with DNA repair systems that can cope with a wide variety of DNA lesions. Among these repair pathways, nucleotide excision repair (NER) is quite versatile, involved in the removal of a variety of bulky DNA lesions induced by ultraviolet light and chemical carcinogens and mutagens. The importance of NER for human health is illustrated mainly by the occurrence of rare life-threatening disorders such as Xeroderma Pigmentosum (XP), Cockayne Syndrome (CS) and Trichthiodystrophy (TTD). XP, CS and most TTD patients exhibit increased sensitivity to UV light and premature aging. XP is associated with a high incidence of skin tumors, CS is primarily a developmental disorder associated with failure to thrive, and psychomotor retardation. The authors report the clinical, biochemical and molecular aspects of the NER pathway in individuals suspected to have a DNA repair, NER type-related disease. These diseases are rare worldwide, but are frequent in Israel, probably due to the high rate of consanguinity among certain Arab, Druze and Jewish populations. Our laboratory is the only one in Israel, and one of very few labs world-wide that is performing DNA repair evaluation as a diagnostic test for DNA repair-deficient inherited diseases. Identification of the causative genes and proteins in suspected families will facilitate accurate diagnosis, genetic counseling, identification of couples at risk and prenatal diagnosis.