REDUCTION OF CGG TRINUCLEOTIDE EXPANSION FROM MOTHER TO OFFSPRING IN 7 FRAGILE-X FAMILIES

Apparent reduction in the size of the CGG repeat is reported from seve n fragile-X mothers to nine offspring in seven extended families. The overall frequency of the reduction amongst 121 fragile-X mother-fragil e-X child transmissions was 7.4%, compared with an 18% reduction in fr agile-X father-fragile-X daughter transmissions, but ascertainment bia s may account for some underestimation of the frequency of reductions, especially between mothers and their offspring. In one mother-son tra nsmission, a premutation present in the son (with a full mutation pres ent in the mother) was unmethylated. This may be the result of either demethylation with reduction, or undetected mosaicism in the mother. T here was no obvious increase in the level of intellectual performance in female offspring who received a reduced fragment from their mothers . Several mechanisms leading to apparent reduction, such as germline m osaicism, deletion or replication slippage, should be considered.