MITOTIC STABILITY OF FRAGILE-X MUTATIONS IN DIFFERENTIATED CELLS INDICATES EARLY POSTCONCEPTIONAL TRINUCLEOTIDE REPEAT EXPANSION

We demonstrate here that somatic variation of CGG repeat length is bas ed on a mosaic of cells with different but stable FMR-1 alleles and do es not reflect permanent mitotic instability. The length of a particul ar allele in an individual cell was maintained in progeny cells establ ishing a clone. The mutation patterns of multiple repeats in the DNA o f fetal tissues were identical and did not significantly change during proliferation in vitro. It is proposed that genotype mosaicism and ex pansion to full mutation are generated postconceptionally by the same molecular mechanism in a particular window of early development.