[Clinical and molecular screening for fragile X syndrome in 300 patients with non-specific mental retardation]

Fragile X syndrome is the most frequent cause of mental retardation linked to the X chromosome. In the majority of cases, the mutation responsible for the syndrome is an expansion of the trinucleotide repeat (CGG)n, present in the 5' region of exon 1 of the gene for mental retardation associated with fragile X syndrome (FMR-1).

To report the results of a fragile X screening in patients with mental retardation.

Fragile X screening using polymerase chain reaction methods was done in 386 X chromosomes from 300 patients (214 male), aged 4 to 26 years old. The modified Hagerman test was applied to male patients. Hybridization techniques were applied in a subgroup of 51 patients.

(CGG)n 30 was the allele found with the highest frequency in 50.2% of patients. (CGG)n 29 was found in 29% of patients. One subject had an allele with 46 CGG repeats, which corresponds to the gray zone. Hybridization studies were highly concordant with PCR, detecting four males with fragile X syndrome and a carrier female. The average clinical score of mental retardation not due to fragile X syndrome was 10.3 +/- 3.4 (range 3 to 23), and 97% of males had a score below 19. The concordance between scores over 20 and molecular genotype was 98%.

The distribution of (CGG)n repeats, observed in this study, was significantly different to that previously reported for a normal Chilean population. The dispersion of molecular status and clinical score was lower than previously described using cytogenetic techniques.