The fragile X syndrome is a leading cause of inherited Mental Retardation(MR). Its prevalemce is 1/1000 males and 1/2500 females. Incidence of carriers in general population is estimated in 1/700. This genic disease, linked to the dominant X chromosome is due to amplification of the region 5′ of FMRI gene, located in the Xq27.3 point. There is a “premutational state” (carriers and No MR) in which the repeat of the unstable CGG is expanded (amplified) but the protein is normally produced. In the “full mutational state”, the repeat of the CGG units is expanded to several hundred copies, there is no protein synthesis and MR appears. Some reports in the literature describe that the carriers of the “premutational state” have a different neurocognitive profile compared with normal controls. The purpose of this clinical research was to define the existence of a “specific” cognitive profile in females carrying the premutational state defined by molecular studies. This data would help professionals involved with learning disabilities suspect the disease. In a period of 6 years we followed 59 pediatric patients with Fragile X Syndrome. 35 families were studied with molecular techniques and 43 females had the premutational state. We describe 21 females (patient's mothers), age: 22-50 years old (X: 36.7) with the premutational state in whom we were able to carry out complete cognitive as well as psychometric studies for adults (WAIS). One female was excluded because of MR due to other genetic condition. IQ profile of the 20 mothers: 5% bordeline; 40% low normal; 35% average normal and 20% in the superior range. None of them had MR. When their cognitive profile was compared with the “standards” described in WAIS, “picture arrangement” and “puzzles” showed average test values below the normal range (p<0.002 and p<0.0001, respectively); in the verbal subtests, “mathematics” displayed a significant difference(p<0.0001). This data correlated well with school performance descriptions Conclusions: Mothers carrying the premutational state have a characteristic cognitive profile. These findings suggest that in females with the premutational state protein synthesis at the cerebral level is inadequate.