title: Detection and Quantification of the Fragile X Mental Retardation Protein 1 (FMRP).
abstract: The final product ofFMR1gene transcription, Fragile X Mental Retardation Protein 1 (FMRP), is an RNA binding protein that acts as a repressor of translation. FMRP is expressed in several tissues and plays important roles in neurogenesis, synaptic plasticity, and ovarian functions and has been implicated in a number of neuropsychological disorders. The loss of FMRP causes Fragile X Syndrome (FXS). In most cases, FXS is due to large expansions of a CGG repeat inFMR1-normally containing 6-54 repeats-to over 200 CGGs and identified as full mutation (FM). Hypermethylation of the repeat inducesFMR1silencing and lack of FMRP expression in FM male. Mosaic FM males express low levels of FMRP and present a less severe phenotype that inversely correlates with FMRP levels. Carriers of pre-mutations (55-200 CGG) show increased mRNA, and normal to reduced FMRP levels. Alternative splicing ofFMR1mRNA results in 24 FMRP predicted isoforms whose expression are tissues and developmentally regulated. Here, we summarize the approaches used by several laboratories including our own to (a) detect and estimate the amount of FMRP in different tissues, developmental stages and various pathologies; and (b) to accurately quantifying FMRP for a direct diagnosis of FXS in adults and newborns.
authors.affiliation: NYS Institute for Basic Research, Staten Island, NY 10314, USA. giuseppe.x.lafauci@opwdd.ny.gov.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: LaFauci
authors.affiliation: NYS Institute for Basic Research, Staten Island, NY 10314, USA. tatyana.adayev@opwdd.ny.gov.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Adayev
authors.affiliation: NYS Institute for Basic Research, Staten Island, NY 10314, USA. richard.kascsak@opwdd.ny.gov.
authors.forename: Richard
authors.initials: R
authors.lastname: Kascsak
authors.affiliation: NYS Institute for Basic Research, Staten Island, NY 10314, USA. ted.brown@opwdd.ny.gov.
authors.forename: W Ted
authors.initials: WT
authors.lastname: Brown
keywords: DBS; ELISA; FMRP; FMRP expression; FXS; TR-FRET; capture immunoassays; newborn screening; western blot