Gonadal mosaicism and familial adenomatous polyposis.
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.
Schwab
Angela L
AL
Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Room 3146, Salt Lake City, UT 84112-5550, USA.
Tuohy
Thérèse M F
TM
Condie
Michelle
M
Neklason
Deborah W
DW
Burt
Randall W
RW
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