Fragile X analysis of 1112 prenatal samples from 1991 to 2010

To determine risks of expansion for normal, intermediate, and premutation FMR1 CGG repeats.

PCR was used to compare the FMR1 alleles in prenatal (chorionic villi and amniocytes) and parental samples collected from 1991 to 2010. Prenatal diagnoses were confirmed by Southern analysis.

Fragile X analysis of 1112 pregnancies identified 558 normal, 106 intermediate, 216 premutation, and 232 full mutation fetuses. Of 509 maternal, intermediate, and premutation alleles, 350 (68.7%) were unstable on transmission with expansions ranging from one repeat to the full mutation. The smallest premutation alleles expanding to the full mutation were in mothers with 65 and 66 repeats. Transmissions from women with or without a family history of fragile X suggested greater instability in women from families that included full mutation expansions.

The maternal transmissions of alleles with 55 to 59 CGG repeats summarized here indicate that the risk for expansion to full mutation is substantially less than previous estimates for this size category. Most premutation alleles with no family history of fragile X exhibited less instability than those with a history of fragile X. Thus, lower risk estimates for full mutation expansion may be appropriate for women newly identified as premutation carriers through routine screening.