The risk of Fragile X premutation expansion is lower in carriers detected by general prenatal screening than in carriers from known Fragile X families

The Fragile X syndrome is the most common cause of inherited mental retarda tion. For a female premutation carrier, the risk of having a child with a f ull mutation is positively correlated with the size of the premutation. The current study was performed to evaluate the risk of premutation expansion in the offspring of average-risk carriers detected by general prenatal scre ening. Over a 4-year period, 9,660 women underwent DNA screening for FMR1 m utation/premutation at the Tel Aviv Sourasky Medical Center, A premutation was defined as a CGG repeat number >50 in the 5' untranslated region (UTR) of exon 1 in the FMR1 gene, The study included only individuals with no fam ily history of X-linked mental retardation or known FMR1 mutations. A premu tation was found in 85 women (1 in 114), 68 of whom consented to have prena tal diagnoses in 74 pregnancies. The abnormal allele was transmitted to the offspring in 44 pregnancies. Of these, no change in allele size was noted in 35 pregnancies (79.6%), and expansion within premutation range was evide nt in 4 pregnancies (9%), In 5 pregnancies (11.4%), expansion to the full m utation was noted. This occurred only in carriers having more than 90 repea ts, We conclude that the likelihood of Fragile X premutation expansion to f ull mutation is significantly lower in individuals ascertained by general p renatal carrier testing than in those from known Fragile X families.