APPARENT REGRESSION OF THE CGG REPEAT IN FMR1 TO AN ALLELE OF NORMAL SIZE

The fragile X syndrome is the result of amplification of a CGG trinucl eotide repeat in the FMR1 gene and anticipation in this disease is cau sed by an intergenerational expansion of this repeat. Although regress ion of a CGG repeat in the premutation range is not uncommon, regressi on from a full premutation (> 200 repeats) or pre mutation range (50-2 00 repeats) to a repeat of normal size (< 50 repeats) has not yet been documented. We present here a family in which the number of repeats a pparently regressed from approximately 110 in the mother to 44 in her daughter. Although the CGG repeat of the daughter is in the normal ran ge, she is a carrier of the fragile X mutation based upon the segregat ion pattern of Xq27 markers flanking FMR1. It is unclear, however, whe ther this allele of 44 repeats will be stably transmitted, as the daug hter has as yet no progeny. Nevertheless, the size range between norma l alleles and premutation alleles overlap, a factor that complicates g enetic counseling.