title: FMRP expression as a potential prognostic indicator in fragile X syndrome.
abstract: Absence or deficit of FMR1 protein (FMRP) resulting from methylation of full mutation genes is the fundamental defect in fragile X syndrome. We used FMRP immunocytochemistry and detailed phenotypic assessment to investigate the relationship between degree of FMRP expression and the broad clinical spectrum of impairment in 80 individuals affected with fragile X syndrome. FMRP expression correlated with IQ in mosaic males (P=0.043), males with a partially methylated full mutation (P=0.0005), and females with a full mutation (P=0.046). In the females, FMRP expression also correlated with the number of fragile X physical features (P=0.0003). Even modest deficits in FMRP result in some manifestations of fragile X syndrome. In this initial study of 53 males, FMRP expression testing had a very high positive predictive value (100%, confidence interval of 29-100%) for a nonretarded IQ among males with expression of FMRP in > or = 50% of lymphocytes (3 males), suggesting that FMRP expression may have potential as a prognostic indicator in males with fragile X syndrome.
authors.affiliation: Kimball Genetics Inc., Child Department Unit, The Children's Hospital, 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: D N
authors.initials: DN
authors.lastname: Iklé
authors.forename: P N
authors.initials: PN
authors.lastname: Dyer
authors.forename: M
authors.initials: M
authors.lastname: Lampe
authors.forename: R
authors.initials: R
authors.lastname: Willemsen
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
authors.forename: A K
authors.initials: AK
authors.lastname: Taylor
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009030:Mosaicism / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D016601:RNA-Binding Proteins
chemical_list: D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human