The FMR-1 gene for the human fragile-chi syndrome, a mental retardation disease inherited by non-Mendelian transmission, contains a genetically unstable CGG region in the 5' non-translated region.
In contrast, a relationship between the second main group of fragile sites characterized by repeat expansion, the rare fragile sites, and mental retardation has been proposed many years ago, but after the molecular cloning of FRAXA and FRAXE both unequivocally involved in mental retardation, no additional fragile sites linked with mental retardation have been cloned for over a decade.
Here we report molecular screening survey of 97 unrelated individuals diagnosed with non-specific mental retardation (MR), which produced positive test for FRAXA in two boys and none positive for the FRAXE mutation.
From the clinical point of view, the folate sensitive rare fragile site FRAXA is the most important fragile site as it is associated with the fragile X syndrome, the most common form of familial mental retardation, affecting about 1/4000 males and 1/6000 females.
The early transcription of FMR-1 gene and the distribution of FMR-1 mRNAs in human fetuses suggest that alterations of FMR-1 gene expression may contribute to the pathogenesis of fragile-X syndrome and especially the mental retardation.
The expression of FRAXA is associated with the fragile X syndrome, the most prevalent form of inherited mental retardation whilst the expression of FRAXE is associated with a rarer and comparatively milder form of mental handicap.
The FRAXE fragile site, 600 kb distal to the more common FRAXA, has been reported to be expressed in subjects with mild non-syndromal mental retardation (MR).
The FRAXE fragile site, 600 Kb distal to the more common FRAXA, has been reported to be expressed in subjects with mild nonsyndromal mental retardation.