The recent identification of an abnormally amplified trinucleotide (cy
tosine guanine guanine) repeat in the fragile X gene (FMR-1) of males
with fragile X syndrome and their carrier mothers allows the study of
the mutation in individuals at risk. In this report, data on 396 patie
nts and 35 normal controls are reported. Included in this sample are p
atients with no known family history of fragile X syndrome or mental r
etardation for whom the risks of fragile X syndrome are unclear. All 3
9 cytogenetically positive affected males and six females had the full
mutation, as represented by a restriction fragment size increase (DEL
TA) of 500 base pairs (bp) or more within the cytosine guanine guanine
repeat-bearing fragment of the FMR-1 gene; and all 16 of the normal o
bligate carrier females bore the premutation, as demonstrated by a DEL
TA of 100 to 500 bp. Of 124 patients (62 males and 62 females) with a
family history of fragile X syndrome, five (8%) of the males and 25 (4
0%) of the females had the premutation. Five (2.2%) of the 231 mentall
y impaired patients with no confirmed family history of fragile X synd
rome were found to have the full mutation. Twelve (33%) of 36 mentally
impaired males and one (20%) of five females with unknown family hist
ory were found to carry an amplified cytosine guanine guanine repeat.
Using this technique, we also reevaluated risk assessments previously
generated by linkage analysis and unambiguously determined the carrier
status of individual family members.