A fragile X case with an amplification/deletion mosaic pattern

Fragile X syndrome is the most common cause of hereditary mental retardatio n. The FMR1 gene, which is involved in fragile X syndrome, contains a polym orphic CGG repeat, which expands in affected patients. Expanding tripler re peats have been shown ro be a new type of mutation, termed "dynamic mutatio n", responsible for more than 12 genetic diseases. These mutations occur as multiple steps rather than as a single event. The first step leads to an u nstable allele that then becomes increasingly unstable generally achieving further increases in copy or occasionally contraction. In this report, we d escribe a fragile X boy with both a hypermethylated full mutation and a del etion of 905 bp encompassing the CGG repeat. The upstream breakpoint is 438 bp 5' to the CGG repeat and the downstream breakpoint is 420 bp 3' of the triplet repeats. The deletion includes the ATG starting codon for translati on of die FMR1 gene. This was confirmed by using FMRP immunocytochemistry b oth on blood smears and hair roots. The deleted region is flanked by a ccgg direct repeat next to the breakpoints: this may have had a critical role i n the formation of a secondary DNA structure leading to the deletion.