Prenatal diagnosis of fragile X syndrome and the risk of expansion of a premutation

The aim of the present study was to evaluate prospectively the dynamics of the FMR1 gene. The risk of full mutation among pregnant women and the carri ers, and the risk of expansion of a premutation allele to a full mutation w ere estimated. We identified 89 pregnant women with an expanded FMR1 gene s eeking prenatal diagnosis. Amniocentesis or chorion villus sampling (CVS) w as offered and a DNA test of the FMR1 gene was carried out in such pregnanc ies. The overall risk of full mutation among women (N = 21) with a repeat s ize between 60 and 80 was 4.8% (one fetus with mosaicism), and the risk of expansion of the premutation allele to a full mutation was 14% in those off spring to whom the premutation allele was transmitted. The risk of full mut ation among the carriers (N = 13) with a repeat size between 81 and 100 was 61.5% (8/13), and the risk of expansion of a premutation allele to a full mutation was 89%. Only one case fell into the category of 101-200 repeats, and expansion to a full mutation was recorded. Fetuses of full mutation mot hers inherited the larger allele in 64% (14/22) of the cases. The range of 40-59 repeats was safe: there were no fetal full mutations. Th e risk of full mutation was also low among the subjects with a repeat size between 60 and 80, whereas the risk increased significantly after 80 repeat s. Maternal premutation size was positively correlated with the risk of hav ing a full mutation offspring.