A fragile X family with high penetrance in females: risk heterogeneity?

A fragile X family is described which shows two interesting features. In a sibship of seven, the two males and four of the five females are affected with mental retardation. Since the only normal daughter is not a carrier, the penetrance of the fragile X mutation in carrier daughters is 100%. Nevertheless, the penetrance of this syndrome in affected daughters of normal mothers has been estimated at a third. Also, DNA typing analysis of flanking RFLP markers revealed a higher than expected number of crossing-overs. We also include the molecular study of the mutation in the (CGG)n repeat of the FMR-1 gene.