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.
Three individuals (2.6%) with the FRAXA form of the fragile X syndrome and one boy (0.9%) with FRAXEmental retardation were detected; a total of four newly diagnosed fragile X families were identified.
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.
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.
With the forthcoming identification of the gene targets that trigger Purkinje cell death in the robotic cerebellum, and the functional conservation among the ALF proteins, the robotic mouse promises to deliver important insights into the pathogenesis of human ataxia, but also of mental retardation to which FMR2 and LAF4 have been linked.
FRAXE syndrome is distinct from fragile X syndrome, a more common genetic form of mental retardation caused by expansion and methylation of a similar repeat in the FMR1 gene located 600 kb proximal to FRAXE.
This review summarises the new data on FRAXE associated mental retardation and the FMR2 gene in the light of the recent discoveries of new genes responsible for other forms of non-specific X-linked mental retardation.
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.
At least seven disorders result from trinucleotide repeat expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X syndromes of mental retardation (FRAXA and FRAXE), myotonic dystrophy, Huntington's disease, spinocerebellar ataxia type 1 (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA).
The presence of a phenotypically normal male with absent FMR2 expression in fibroblasts suggests that the relationship between the FRAXE mutation, FMR2 expression and MR needs to be further investigated.
These results suggest that neither the FMR1 nor the FMR2 mutation is a common etiology of academic failure among school-age children without mental retardation and that the prevalence of the FMR1 premutation is no more frequent in children with academic failure than it is in the general population.
We examined the prevalence of the fragile X mental retardation (FMR1) full mutation and fragile X E mutation (FMR2) among preschoolers evaluated for language delay.