title: Examination of FMR1 transcript and protein levels among 74 premutation carriers.
abstract: Fragile X-associated disorders are caused by a CGG trinucleotide repeat expansion in the 5'-untranslated region of the FMR1 gene. Expansion of the CGG trinucleotide repeats to >200 copies (that is, a full mutation) induces methylation of the FMR1 gene, with transcriptional silencing being the eventual outcome. Previous data have shown that FMR1 premutation carriers (individuals with 55-199 repeats) have increased FMR1 mRNA levels with decreased protein (fragile X mental retardation protein (FMRP)) levels. However, the point at which this translational inefficiency occurs, given the increased transcription mechanism, has not yet been explored and remains to be elucidated. We examined the repeat length group, FMR1 transcript and FMRP levels in 74 males with a wide range of repeat lengths using analysis of covariance to better characterize this association. Results showed that the mean FMRP level among carriers with 80-89 repeats was significantly higher than the mean levels among lower (54-79) and higher (90-120) premutation carriers, in spite of the increasing transcript level with repeat length. Taken together, these results suggest that the 80-89-repeat group may lead to different properties that increase the efficiency of translation compared with other premutation repeat size groups.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA. epeprah@emory.edu
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Peprah
authors.forename: Weiya
authors.initials: W
authors.lastname: He
authors.forename: Emily
authors.initials: E
authors.lastname: Allen
authors.forename: Tiffany
authors.initials: T
authors.lastname: Oliver
authors.forename: Alex
authors.initials: A
authors.lastname: Boyne
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Sherman
mesh_terms: D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D019680:Trinucleotide Repeat Expansion; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; C497683:FMR1 protein, human