UNSTABLE TRIPLETS AND THEIR MUTATIONAL MECHANISM - SIZE-REDUCTION OF THE CGG REPEAT VS GERMLINE MOSAICISM IN THE FRAGILE-X-SYNDROME

The mechanism responsible for the characteristic expansion of the trin ucleotide repeat peat involved in the pathogenesis of the fragile X sy ndrome is still largely unclear. Slipped strand mispairing (SSM) and s imilar DNA replication errors could determine both increases and decre ases of the unit number in simple repetitive sequences. Actually, ther e have been a few reports of size reduction of the (CGG)(n) in parent- to-child transmission of the fragile X syndrome, which may help in und erstanding the mutational mechanism and may have practical implication s for genetic counseling. We describe here 5 such cases from our serie s of fragile X patients and emphasize the possible role of SSM-like ev ents in causing (CGG)(n) expansions and reductions. The possibility th at some of these reductions are only apparent, resulting from parental germinal mosaicism is also considered. (c) 1994 Wiley-Liss,Inc.