Objectives: We have screened the FMR1 locus in one proband from each of 1742 families.
Methods: Standard Molecular Methods were employed
Results: We found 8 families that had the fragile X mutation present. Among these, 6 were found among the first set of 480 families. The prevalence of fragile X among the ~312 AGRE families that had had no prior genetic screening was ~ 1.9%. An estimate of the IQ score of the autistic subjects was 80±35 with range 34-144, based on Raven and Stanford-Binet testing. Thus, the AGRE sample is likely to have a higher IQ distribution than typical for fragile X subjects (mean ~40±25). Previous prevalence studies of fragile X in autistic samples range from 0 to 16%; with a mean of ~4%; (Feinstein 98). Our 1.9% is similar to a report of 1.6% among 123 unrelated autistic individuals (Bailey 93), but lower than the 13% we found on an earlier multicenter study of 183 individuals (Brown 86). A growing awareness of fragile X syndrome has decreased the probability of fragile X in these multiplex autism families due to screening and exclusion from AGRE. The observed frequency of 1.9% is lower than the expected 4%, perhaps due to higher IQs in AGRE subjects than is typical for fragile X. This finding confirms an association of fragile X and autism.
Conclusions: We tested to see if there is an association of autism and permutations or intermediate alleles. Among the 1535 male probands tested, there were 2 with premutation (59 & 64 CGGs) and 12 with intermediate (45-54 CGGs) alleles (46, 47, 47, 47, 48, 48, 48, 49, 50, 50, 51, 54) for an intermediate prevalence of 0.78%. Among the 206 female probands tested there were 2 with premutations (55, 59) and 7 with intermediate alleles (45, 46, 48, 50, 52, 53, 54). Since females have two alleles, dividing by 2 gives an intermediate allele prevalence of 1.7% in female alleles or an overall intermediate allele prevalence of 0.98%. Our published control value for 2500 X chromosomes was 1.7% (Brown 96), and our more recent control value based on carrier screening of 9064 X chromosomes was 1.15%. Thus, there was no excess of intermediate or premutation alleles among the AGRE registry autistic probands. This finding suggests autism is NOT associated with intermediate (45-54) or premutation (55-200) alleles.
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