Analysis of the FMR-1 gene and correlation with phenotype in Sicilian families with the fragile X syndrome

Fragile X (FRAXA) or Martin-Bell (MB) syndrome is a common inherited form of mental retardation (MR). Diagnosis relies on the appearance of MR of variable degree and several dysmorphic features usually involving the connective tissue. However, identification of Martin-Bell (MB) patients may be difficult because the FRAXA clinical phenotype shows variable expressivity. A similar consideration also concerns the degree of expression of the fragile site in Xq27.3 on which cytogenetic diagnosis relies. The prevalence is estimated to be 1 in 1,250 males and 1 in 2,500 females (1, 2). Unexpectedly, for an X-linked trait, normal transmitting males (NTMs) have been described in fragile X pedigrees. Furthermore, the risk of manifesting the MB phenotype depends on the position of affected individuals in the pedigree. The latter observation is also known as the Sherman's paradox (3, 4). In the present study me report the results of FMR-1 gene analysis with probe StB12.3 (5) in mentally retarded individuals and relatives evoking the phenotype of MB syndrome. In order to exploit the potential use of DNA analysis for predicting the fragile X phenotype, a preliminary analysis on the correlation between mutation severity (triplet expansion) and cytogenetic expression has been carried out.