SCREENING FOR FMR1 AND FMR2 MUTATIONS IN 222 INDIVIDUALS FROM SPANISHSPECIAL SCHOOLS - IDENTIFICATION OF A CASE OF FRAXE-ASSOCIATED MENTAL-RETARDATION

Fragile X syndrome is the most common inherited form of familial menta l retardation. It results from a (CGG)(n) trinucleotide expansion in t he FMR1 gene leading to the typical Martin-Bell phenotype. Clinical fe atures vary depending on age and sex. Expansion of a (CCG)(n) repeat i n the FMR2 gene corresponds to the FRAXE fragile site which lies dista l to FRAXA and is also associated with mental retardation, but it is l ess frequent and lacks a consistent phenotype. Analysis of repeat expa nsions in these two genes allows the molecular diagnosis of these diff erent entities. We report here the screening of the FRAXA and FRAXE mu tations in 222 unrelated mentally retarded individuals attending Spani sh special schools. PCR and/or Southern blotting methods were used. We detected full mutations in the FMR1 gene in 11 boys (4.9%) and 1 boy (0.5%) with a CCG repeat expansion in the FMR2 gene. The latter shows mild mental retardation with psychotic behaviour and no remarkable phy sical traits. Molecular studies revealed a mosaicism for methylation i n the FMR2 gene. This case supports the observation that expansions gr eater than 100 repeats can be partially methylated and cause the pheno type.