Strong similarities of the FMR1 mutation in multiple tissues: postmortem studies of a male with a full mutation and a male carrier of a premutation.

Studies of the FMR1 mutation in multiple tissues are important to further our understanding of CGG repeat expansion in development and of the frequency and possible clinical significance of inter-tissue heterogeneity in fragile X syndrome. With some exceptions, most cases reported have shown strong similarity of the mutation size and methylation status between tissues. However, there have been only a few studies of multiple tissues including regions of the brain. We report on two postmortem studies of multiple tissues, one of a male with a full mutation (fully methylated) and one of a male carrier of a premutation. The male with the full mutation (TH) had a typical presentation of fragile X syndrome, including mild mental retardation. He had a methylated full mutation of two predominant sizes in all 12 tissues analyzed, including three regions of the brain. The male carrier of a premutation (GC) was clinically unaffected, and the mutation was the same size in all 14 tissues examined including seven regions of the brain. Therefore, both cases demonstrated lack of inter-tissue heterogeneity, suggesting strong somatic stability after the period of expansion to the observed mutation size(s). Also, both cases showed consistency between clinical phenotype and mutation characteristics in the brain.