title: 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.
abstract: 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.
authors.affiliation: Kimball Genetics, Inc., Denver, Colorado 80206, USA.
authors.forename: F
authors.initials: F
authors.lastname: Tassone
authors.forename: R J
authors.initials: RJ
authors.lastname: Hagerman
authors.forename: L W
authors.initials: LW
authors.lastname: Gane
authors.forename: A K
authors.initials: AK
authors.lastname: Taylor
mesh_terms: D000328:Adult; D004247:DNA / Q000032:analysis; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics*; D016601:RNA-Binding Proteins; D014018:Tissue Distribution
chemical_list: D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human