We demonstrated that increased methylation of the FMR1 intron 1 sites, specifically CpG10–12, located within FREE2(A) was associated with an increased CGG size within the FM range in males, with its analytical superiority to methylation-sensitive Southern blot (used in current FXS diagnostics) and FMRP immunostaining in the blood as a predictor of cognitive impairment in females with an FM [3,14,21] and the dysexecutive-psychiatric phenotype in adult females with PM alleles. The gene discussed is FMR1; the disease is fragile X syndrome.