LOSS OF MUTATION AT THE FMR1 LOCUS THROUGH MULTIPLE EXCHANGES BETWEENMATERNAL X-CHROMOSOMES

The mutation observed in the fragile X syndrome, an X-linked inherited disorder causing mental retardation, is almost exclusively an expande d CGG repeat in the first exon of the FMR1 gene. Here we describe a da ughter of a female carrier, who inherited the fragile X premutation ch romosome based on haplotype analysis using flanking markers. However, the CGG repeat sequence and the intragenic polymorphic marker FMRb sho wed the normal maternal alleles, while two other intragenic markers, F MRa and FRAXAC2 and other, more distant markers, showed the risk haplo type. Since FMRa and FRAXAC2 are located in between the markers CGG an d FMRb, this results in patches of normal and fragile X sequences in t he FMR1 gene of the daughter. This observation is very likely due to g ene conversion. As this daughter received a normal CGG repeat region, we expect that her risk to have affected offspring is the same as the population risk. The observed phenomenon would therefore represent a b ack mutation at the FMR1 locus.