EXPANSION OF THE CGG REPEAT IN FRAGILE-X IN THE FMR1 GENE DEPENDS ON THE SEX OF THE OFFSPRING

Analysis of 139 mother-to-offspring transmissions of fragile X CGG tri plet repeats revealed that the repeat expansion is enhanced in mother- to-son transmissions compared with mother-to-daughter transmissions. E vidence has been based on analysis of mother-offspring differences in the size of repeat (in kb), as well as on comparisons between proporti ons of male and female offspring with premutations, and full mutations , inherited from mothers carrying a premutation. Mean difference in th e repeat size from mother-son transmissions was 1.45 kb, compared with mother-daughter transmissions of 0.76 kb. The difference is due prima rily to a greater proportion of male than female offspring with full m utation from the premutation mothers and also to a higher frequency of reduction in repeat size from mothers to daughters than from mothers to sons. Our findings suggest the possibility of an interaction of the normal X homologue in a female zygote with the FMR1 sequence on the f ragile X during replication to account for the lower level of expansio n in mother-to-daughter transmissions relative to mother-to-son transm issions.