MOLECULAR CHARACTERIZATION OF FRAXE-POSITIVE SUBJECTS WITH MENTAL IMPAIRMENT IN 2 UNRELATED ITALIAN FAMILIES

The FRAXE fragile site, 600 Kb distal to the more common FRAXA, has be en reported to be expressed in subjects with mild nonsyndromal mental retardation. Amplification of more than 200 GCC repeats associated wit h methylation of the adjacent CpG island at Xq28 is responsible for FR AXE fragility. We describe two unrelated, mentally retarded males iden tified during a screening for fragile X syndrome, Both index cases und erwent FRAXE molecular analysis, following cytogenetic expression of t he fra X site and negative FRAXA test, In family 1, we were able to in vestigate other 13 subjects over three generations, identifying two ad ditional FRAXE-positive males, one with a fully mutated allele and one with a mosaic genotype, Detailed evaluation of physical traits and ps ychometric tests was pet-formed on three retarded males fi-om family 1 and the propositus hom family 2, All of them were found to lack a def inite phenotype, and showed different degrees of mental retardation, S light mental retardation was evident in the mosaic male, suggesting th at methylation might be an important. determinant of mental impairment . (C) 1998 Wiley-Liss, Inc.