title: Gonadal mosaicism and familial adenomatous polyposis.
abstract: 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.
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Room 3146, Salt Lake City, UT 84112-5550, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Schwab
authors.forename: Thérèse M F
authors.initials: TM
authors.lastname: Tuohy
authors.forename: Michelle
authors.initials: M
authors.lastname: Condie
authors.forename: Deborah W
authors.initials: DW
authors.lastname: Neklason
authors.forename: Randall W
authors.initials: RW
authors.lastname: Burt
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000483:Alleles; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006060:Gonadal Dysgenesis, Mixed / Q000235:genetics*; D006801:Humans; D008297:Male; D009030:Mosaicism; D009154:Mutation; D010375:Pedigree; D012307:Risk Factors; D035781:Siblings