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 in ter-tissue heterogeneity and possible clinical implications of this finding , fibroblast cells from the subject were also studied. Although the premuta tion size was found to be the same in leukocytes and fibroblasts, the methy lation 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. Howe ver, the change in methylation did not affect the FMR1 protein (FMRP) expre ssion, as immunocytochemical analysis of FMRP performed on cultured skin fi broblasts and a blood smear revealed normal levels of expression in both ti ssues.