A STUDY OF FRAXE IN MENTALLY-RETARDED INDIVIDUALS REFERRED FOR FRAGILE-X SYNDROME (FRAXA) TESTING IN THE UNITED-KINGDOM

The folate-sensitive fragile site FRAXE is located in proximal Xq28 of the human X chromosome and lies similar to 600 kb distal to the fragi le X syndrome (FRAXA) fragile sire at Xq27.3. The cytogenetic expressi on of FRAXE is thought to be associated with mental handicap, but this is usually mild compared to that of the more common fragile X syndrom e that is associated with the expression of the FRAXA fragile site. Th e exact incidence of FRAXE mental retardation is uncertain. We describ e here the results of a U.K. survey designed to assess the frequency o f FRAXE in a population of individuals referred for fragile X syndrome testing and found to be negative for expansion events at the FRAXA lo cus. No FRAXE expansion events were found in 362 cytogenetically negat ive males studied, and one expansion event was identified in a sample of 534 males for whom cytogenetic analyses were either unrecorded or n ot performed. Further FRAXE expansion events were detected in two rela ted females known to be cytogenetically positive for a fragile site in Xq27.3-28. To gain insight into the FRAXE phenotype, the clinical det ails of the identified FRAXE male plus three other FRAXE individuals i dentified through previous referrals for fragile X syndrome testing ar e presented. For the population studied, we conclude that FRAXE mental retardation is a relatively rare but significant form of mental retar dation for which genetic diagnosis would be appropriate.