Tissue-specific methylation differences in a fragile X premutation carrier

Methylation of a premutation was found in a small percentage of blood cells in a male premutation carrier for the FMR1 mutation. To investigate the inter-tissue heterogeneity and possible clinical implications of this finding, fibroblast cells from the subject were also studied. Although the premutation size was found to be the same in leukocytes and fibroblasts, the methylation pattern was different. In cultured fibroblasts, the premutation was completely unmethylated, as is typical of premutations, whereas methylation of the premutation was detected in a small percentage of lymphocytes. However, the change in methylation did not affect the FMR1 protein (FMRP) expression, as immunocytochemical analysis of FMRP performed on cultured skin fibroblasts and a blood smear revealed normal levels of expression in both tissues.