Somatic gene mutation and human disease other than cancer

Mutat Res. 2003 Mar;543(2):125-36. doi: 10.1016/s1383-5742(03)00010-3.


While the focus of much mutation research is on germ-line mutation, somatic mutation is being found to be important in human disease. Neurofibromatosis 1 and McCune-Albright are disorders which are detected in the skin and other systems. The skin manifestations were essential for the demonstration of somatic mosaicism in neurofibromatosis 1, while analysis of blood DNA demonstrated somatic mutation in neurofibromatosis 2. Incontinentia pigmenti is also a disorder seen in skin and other tissues, but here it is the rare variant of the disorder in males, where it is usually lethal, that involves somatic mosaicism. Paroxysmal nocturnal hemoglobinuria is a disorder of the blood and cell separation of blood elements allows the demonstration of the somatic mosaicism. This review also discusses disorders in which somatic mosaicism, for mutations probably incompatible with life if the mutation had been germ-line, are likely to be involved. These include the Proteus syndrome, which involves both vascular tissues and bones, and two disorders which might be thought of as representing two subtypes of Proteus: Klippel-Trenaunay, which involves vascular tissues, and Maffuci, which involves bones. Embryonic mutations, which create mosaicism for both the soma and germ-line, are being increasingly found in a number of disorders and are discussed more briefly. Finally, reverse mutations involving the soma have been recently found in several disorders and such revertant mutations are also examined. While the review focuses on the clinical importance of somatic mutations, many of the mutations found to date are tabulated. It is too early to see if there is a different pattern of somatic mutation as compared to germ-line mutation. Although the parameters to allow careful quantitation are not yet available, it seems that the frequency of gene mutation in embryonic cells is not markedly different than that in the germ-line.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Fibrous Dysplasia, Polyostotic / genetics
  • Genetic Diseases, Inborn / genetics*
  • Humans
  • Incontinentia Pigmenti / genetics
  • Male
  • Mosaicism
  • Mutation*
  • Neurofibromatoses / genetics
  • Proteus Syndrome / genetics