No apparent involvement of the FMR1 gene in five patients with phenotypic manifestations of the fragile X syndrome.

Most fragile X patients have a significant increase in the number of CGG repeats in the FMR1 gene. Two patients were described with a deletion and one patient with a point mutation in the FMR1 gene. We describe 5 patients with a fragile X or Martin-Bell phenotype. Two brothers were discordant for the region containing the FMR1 gene; if there is a common cause for the mental retardation this is not located in the FMR1 gene. In the other 3 patients the expression of the FMR1 gene was found to be normal and no abnormalities were noted in the FMR1 mRNA. No amplification was found in the GCC repeat which is associated with the fragile site FRAXE. We conclude that the Martin-Bell phenotype can also be caused by mutations outside the FMR1 gene.