Analysis of a CGG sequence at the FMR-1 locus in fragile X families and in the general population.

摘要: In this study, we have characterized a CGG repeat at the FMR-1 locus in more than 100 families (more 500 individuals) presenting for fragile X testing and 247 individuals from general population. Both Southern blot PCR-based assays were evaluated their ability to detect premutations, full mutations, variability normal allele sizes. Among assays, probes Ox1.9 or StB12.3 with double restriction-enzyme digest most sensitive detecting both small large amplifications and, addition, provided information on methylation of an adjacent CpG island. analysis PCR products denaturing DNA sequencing gels allowed accurate determination number up approximately 130 repeats. A combination assay PCR-sequencing-gel detected spectrum amplification-type mutations locus. patient population, 51 was largest be stably inherited, 57 smallest size premutation unstably inherited. When premutations transmitted by females, correlated risk expansion mutation next generation. Full (large repeats typically associated abnormal pattern mitotic instability) clinical cytogenetic manifestations males but not necessarily females. control ranged 13 61, 94% alleles had fewer 40 The frequent (34%) 30. One female (61 repeats) within range consistent while two other each 52. This suggests that frequency unstable population may 1%.