Somatic gene mutation and human disease other than cancer: an update

Mutat Res. 2010 Oct;705(2):96-106. doi: 10.1016/j.mrrev.2010.04.002. Epub 2010 Apr 24.


Somatic mosaicism is well known in disorders where the manifestations are readily seen, e.g. the skin in neurofibromatosis I. In single gene disorders of higher frequency, especially X-linked ones, the frequency of combined germ-line and somatic mosaicism is increasingly being appreciated, e.g. Duchenne Muscular Dystrophy. Cell separation techniques; such as the fluorescence-activated cell sorter (FACS) also detect much somatic mosaicism among blood cells in disorders such as paroxysmal nocturnal hemoglobinuria. Depending on the disorder and the class of mutation, in genes for which there are sufficient numbers of patients studied, 6-20% of cases are due to somatic mutation. This update of my previous review is stimulated by the rapid application of new technologies for the study of DNA variation in disease. The results of these studies implicate somatic mutation in a greater variety of genetic diseases and a wider spectrum of tissues than have previously been shown, including heart and kidney. The classes of mutation have also expanded beyond base pair changes, insertions/deletion (indels), and short tandem repeat mutations to include copy number variants and transposon-mediated mutations. I also briefly discuss previously well-known mosaicism for chromosomal mutations. Genomic sequencing, performed on DNA from blood, shows many mutations which are conclusively somatic in origin. It is still too early to see if there is a different pattern of somatic mutation compared to germ-line mutation. Though the parameters to allow careful quantification 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

  • Aneuploidy
  • DNA Copy Number Variations
  • Genetic Diseases, Inborn* / genetics
  • Germ-Line Mutation
  • Humans
  • Mosaicism*
  • Mutation*
  • Sequence Analysis, DNA