Gonadal mosaicism and familial adenomatous polyposis

Fam Cancer. 2008;7(2):173-7. doi: 10.1007/s10689-007-9169-1. Epub 2007 Nov 18.


De novo mutations in the adenomatous polyposis coli (APC) gene are estimated to constitute approximately 25% of familial adenomatous polyposis (FAP) cases. A small percentage of these arise in the mosaic form, affecting only a subset of cells in the affected individual. A family is described here whereby an unaffected mother with no detectible mutation in APC, transmitted the identical APC c.4729G>T (p.Glu1577X) mutation to two children. A third child, with the same APC allelic haplotype received a normal APC allele, suggesting that the mutation originated in the gonadal tissues of the mother. These results underscore the utility of mutation-specific genetic testing for the parents and siblings of a proband of an adult-onset disease, even if the proband appears to have a de novo mutation. Parents who test negative for the mutation should be counseled about the possibility of having another affected child due to gonadal mosaicism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenomatous Polyposis Coli / genetics*
  • Alleles
  • Female
  • Genetic Testing
  • Genotype
  • Gonadal Dysgenesis, Mixed / genetics*
  • Humans
  • Male
  • Mosaicism*
  • Mutation
  • Pedigree
  • Risk Factors
  • Siblings