Unstable mutations in vitiligo, organ-specific autoimmune diseases, and multiple endocrine adenoma/peptic-ulcer syndrome.
A study of patients with vitiligo shows that the pattern of depigmentation is genetically determined. The mutant gene, however, is unstable in that it often does not breed true even in identical twins or on the two sides of the body in an individual. The patchiness of vitiligo is probably due to activation of the mutant gene in discrete clones of cells which govern melanocyte behaviour at the sites of pigment loss. The frequent occurrence of different organ-specific autoimmune diseases in various members of a single family could also be attributable to unstable mutations in a set of genes which control endocrine and gastric epithelial cells; activation of the mutant gene in particular cell clones may account for the focal tissue damage often associated with, but not readily explained by, organ specific autoimmunity. Unstable mutation causing cell proliferation seems to affect the same set of genes in families with the multiple endocrine adenoma-peptic ulcer syndrome, the occurrence of focal (adenoma) or diffuse dyperplasia depending on the size of the cell clones in which the mutant genes have been activated. The tendency of these genes to display unstable mutations which subsequently undergo further mutation is reminiscent of the behavior of certain linked genes in special chromatosomal regions in plants, insects, and mice and may provide clues to the association of histocompatibility antigens with certain diseases in man.
D000328:Adult; D001327:Autoimmune Diseases / Q000235:genetics*; D002648:Child; D004200:Diseases in Twins; D005260:Female; D005796:Genes; D006801:Humans; D008297:Male; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D009154:Mutation; D009928:Organ Specificity; D010437:Peptic Ulcer / Q000235:genetics*; D010860:Pigments, Biological / Q000235:genetics / Q000378:metabolism; D013577:Syndrome; D014820:Vitiligo / Q000235:genetics*
D010860:Pigments, Biological