MOSAICISM IN FRAGILE-X AFFECTED MALES

Fragile X affected males have an expansion of a CGG repeat and a hyper methylated CpG island 5 ' to the FMR-1 gene. Mosaic males with both a premutation and full mutation have been noted among the affected indiv iduals. Such mosaic males are most easily identified by the presence o f a methylated restriction fragment characteristic of the full mutatio n and an additional unmethylated fragment in the premutation range in Southern analyses with EcoR I and the methylation-sensitive enzyme fag I and a probe such as StB12.3. We analyzed a group of affected fragil e X males by Southern blotting and found 41% (61/148) to be mosaic. Th e 148 individuals were divided between 36 pairs of brothers and 76 unr elated males. Little difference in the number of mosaics was seen betw een the brothers and the unrelated males nor was the expected distribu tion of mosaicism in brother pairs different from observed. Thus, thes e data do not suggest a familial basis for mosaicism. Our observation that 41% affected fragile X males were mosaic is significantly higher than previous reports. The difference is likely due to technical modif ications which permitted the identification of faint premutation bands in some patients. The high percentage of affected males with mosaicis m seen here suggests that the occurrence of such individuals may be a much more frequent event than presently recognized. (c) 1994 Wiley-Lis s, Inc.