Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and autism. The FMR1 gene contains a CGG repeat present in the 5'-untranslated region which can be unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In patients with fragile X syndrome (FXS), a repeat length exceeding 200 CGGs generally leads to methylation of the repeat and the promoter region, which is accompanied by silencing of the FMR1 gene. The disease is a result of lack of expression of the fragile X mental retardation protein leading to severe symptoms, including intellectual disability, hyperactivity, and autistic-like behavior. The FMR1 protein (FMRP) has a number of functions. The translational dysregulation of a subset of mRNAs targeted by FMRP is probably the major contribution to FXS. FMRP is also involved in mRNA transport to synapses where protein synthesis occurs. For some FMRP-bound mRNAs, FMRP is a direct modulator of mRNA stability either by sustaining or preventing mRNA decay. Increased knowledge about the role of FMRP has led to the identification of potential treatments for fragile X syndrome that were often tested first in the different animal models. This review gives an overview about the present knowledge of the function of FMRP and the therapeutic strategies in mouse and man.

Bagni, C., Oostra, (2013). Fragile X syndrome: From protein function to therapy. AMERICAN JOURNAL OF MEDICAL GENETICS. PART A, 161(11), 2809-2821 [10.1002/ajmg.a.36241].

Fragile X syndrome: From protein function to therapy

BAGNI, CLAUDIA
;
2013-01-01

Abstract

Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and autism. The FMR1 gene contains a CGG repeat present in the 5'-untranslated region which can be unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In patients with fragile X syndrome (FXS), a repeat length exceeding 200 CGGs generally leads to methylation of the repeat and the promoter region, which is accompanied by silencing of the FMR1 gene. The disease is a result of lack of expression of the fragile X mental retardation protein leading to severe symptoms, including intellectual disability, hyperactivity, and autistic-like behavior. The FMR1 protein (FMRP) has a number of functions. The translational dysregulation of a subset of mRNAs targeted by FMRP is probably the major contribution to FXS. FMRP is also involved in mRNA transport to synapses where protein synthesis occurs. For some FMRP-bound mRNAs, FMRP is a direct modulator of mRNA stability either by sustaining or preventing mRNA decay. Increased knowledge about the role of FMRP has led to the identification of potential treatments for fragile X syndrome that were often tested first in the different animal models. This review gives an overview about the present knowledge of the function of FMRP and the therapeutic strategies in mouse and man.
2013
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13 - BIOLOGIA APPLICATA
English
FMR1; FMRP; Fmr1 KO mouse; fragile X syndrome; intellectual disability; protein function; review; treatment; Animals; Disease Models, Animal; Fragile X Mental Retardation Protein; Fragile X Syndrome; GABA Agonists; Gene Expression Regulation; Humans; Molecular Targeted Therapy; Receptors, Metabotropic Glutamate; Signal Transduction
Bagni, C., Oostra, (2013). Fragile X syndrome: From protein function to therapy. AMERICAN JOURNAL OF MEDICAL GENETICS. PART A, 161(11), 2809-2821 [10.1002/ajmg.a.36241].
Bagni, C; Oostra,
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/244789
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