title: Diseases of DNA repair.
abstract: A number of disparate clinical syndromes have been loosely grouped together under the leading of diseases of DNA repair. More logically they should perhaps be termed diseases of diminished capacity to cope with DNA damage, since in only three has defective DNA repair been established as a basis so far. These are xeroderma pigmentosum, ataxia telangiectasia and Fanconi's anaemia. Increased sensitivity may be to radiation, to particular types of chemical mutagens, or to both. This sensitivity may be reflected in an increased liability to chromosome aberrations, decreased cell survival in culture and, in some cases only, increased mutagenesis. In many cases there is an associated increased liability to develop malignant tumours. These syndromes are genetically autosomal recessive so that it is the relatively rare homozygotes which display the full clinical picture. In some cases, however, the heterozygotes share the increased liability to cancer: since these are of relatively high frequency, they may be quantitatively important in the genetics of some human cancers including leukaemias. Immunological abnormalities are common and frequently are selective. This suggests the possibility that the repair systems whose defects are monitored by decreased capacity to cope with DNA damage may also perform functions essential to differentiation during embryonic development. At a molecular level knowledge of the fundamental defects in each of these groups of human mutants is still rudimentary. There is sufficient evidence, however, to conclude that each group is genetically heterogeneous, involving more than one gene locus, so that the total number of genes involved is probably large.
mesh_terms: D000328:Adult; D001260:Ataxia Telangiectasia / Q000235:genetics; D002470:Cell Survival; D002869:Chromosome Aberrations; D004261:DNA Replication; D004274:DNA, Recombinant; D005199:Fanconi Anemia / Q000235:genetics; D005347:Fibroblasts; D030342:Genetic Diseases, Inborn; D006130:Growth Disorders / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology; D009656:North America; D013577:Syndrome; D013684:Telangiectasis / Q000235:genetics; D014983:Xeroderma Pigmentosum / Q000235:genetics
chemical_list: D004274:DNA, Recombinant; D009153:Mutagens