INSTABILITY OF THE FMR2 TRINUCLEOTIDE REPEAT REGION ASSOCIATED WITH EXPANDED FMR1 ALLELES

The fragile sites FRAXA and FRAXE, located similar to 600 kb apart on Xq27.3 and Xq28, respectively, are due to a CGG trinucleotide repeat e xpansion. Although the expansion mechanism for these and other trinucl eotide repeat disorders remains unknown, the similarities between the FRAXA and FRAXE regions suggest a possible association between the 2 s ites. DNA from 953 individuals was analyzed to determine the distribut ion of FRAXE repeat sizes in this population and to ascertain potentia l association between FRAXA and FRAXE repeat sizes, Thirty-four FMR2 a lleles ranging from 3-42 repeats were identified. No FRAXE expansions were found in this population, supporting previous findings that FRAXE expansions are rare. However, in the fragile X syndrome affected grou p, a FMR2 delection, 2 cases of FRAXE repeat instability and a FRAXE m osaic male were identified, Also, a previously identified, rare FMR2 p olymorphism was observed, Statistical analyis showed no correlation be tween normal FRAXA and FRAXE repeat sizes studied, although there was a significant size difference in larger FMR2 alleles that segregated w ith expanded FMR1 alleles, These findings support the idea of an assoc iation between repeat expansion in the FMR1 gene and instability or de letions in the FMR2 gene. (C) 1997 Wiley-Liss, Inc.