The fragile X syndrome is a common cause of mental impairment. In view
of the low reproductive fitness of affected males, the high incidence
of the syndrome has been suggested to be the result of a high rate of
new mutations occurring exclusively in the male germline. Extensive f
amily studies, however, have failed to identify any cases of a new mut
ation. Alternatively, it has been suggested that a selective advantage
of unaffected heterozygotes may, in part, explain the high incidence
of the syndrome. Molecular investigations have shown that the syndrome
is caused by the amplification of a CGG trinucleotide repeat in the F
MR-1 gene which leads to the loss of gene expression. Further to this,
genetic studies have suggested that there is evidence of linkage dise
quilibrium between the fragile X disease locus and flanking polymorphi
c markers. More recently, this analysis has been extended and has led
to the observation that a large number of fragile X chromosomes appear
to be lineage descendants of founder mutation events. Here, we presen
t a study of the FRAXAC1 polymorphic marker in our patient cohort. We
find that its allele distribution is strikingly different on fragile X
chromosomes, confirming the earlier observations and giving further s
upport to the suggestions of a fragile X founder effect.