CLINICAL, CYTOGENETIC, AND MOLECULAR ANALYSIS OF 3 FAMILIES WITH FRAXE

The probe StB12.3 has been used to screen the FMR-1 gene in 42 pedigre es with a distal Xq fragile site for expansion of the CCG repeat and a berrant methylation of the FRAXA locus. Four families did not have a F RAXA mutation and were investigated further. Fluorescent in situ hybri disation (FISH) and molecular analyses showed that three of these fami lies had an expansion at FRAXE and one at FRAXF. Detailed psychiatric, psychological, and behavioural features of three families with FRAXE identified in the study are presented. All the males who expressed FRA XE had a large methylated CCG repeat at FRAXE. All males with the muta tion had some degree of mental handicap. This study illustrates the ne ed for the FRAXE phenotype to be defined further.