Twin sisters, monozygotic with the fragile X mutation, but with a different phenotype

The absence of the fragile X mental retardation protein (FMRP) results in fragile X syndrome. All males with a full mutation in the FMR1 gene and an inactive FMR1 gene are mentally retarded while 60% of the females with a full mutation are affected. Here we describe monozygotic twin sisters who both have a full mutation in their FMR1 gene, one of whom is normal while the other is affected. Using molecular and protein studies it was shown that owing to preferential X inactivation in the affected female a minority of the cells expressed the normal FMR1 gene, while in her sister most cells expressed the normal FMR1 gene. This shows that X inactivation took place in the female twins after separation of the embryos and that for a normal phenotype FMR1 expression is necessary in the majority of cells.