The mGluR5 antagonist AFQ056 does not affect methylation and transcription of the mutant FMR1 gene in vitro.
BMC Med Genet
; 13: 13, 2012 Mar 07.
Article
em En
| MEDLINE
| ID: mdl-22397687
ABSTRACT
BACKGROUND:
Fragile X syndrome (FXS), the leading cause of inherited mental retardation, is due to expansion and methylation of a CGG sequence in the FMR1 gene, which result in its silencing and consequent absence of FMRP protein. This absence causes loss of repression of metabotropic glutamate receptor 5 (mGluR5)-mediated pathways resulting in the behavioral and cognitive impairments associated with FXS. In a randomized, double-blind trial it was recently demonstrated a beneficial effect of AFQ056, a selective inhibitor of metabotrobic glutamate receptor type 5 (mGluR5), on fully methylated FXS patients respect to partially methylated FXS ones.METHODS:
To determine whether AFQ056 may have secondary effects on the methylation and transcription of FMR1, here we treated three FXS lymphoblastoid cell lines and one normal control male line. A quantitative RT-PCR was performed to assess transcriptional reactivation of the FMR1 gene. To assess the methylation status of the FMR1 gene promoter it was carried out a bisulphite sequencing analysis.RESULTS:
Both FMR1-mRNA levels and DNA methylation were unmodified with respect to untreated controls.CONCLUSIONS:
These results demonstrate that the AFQ056 effect on fully methylated FXS patients is not due to a secondary effect on DNA methylation and consequent transcriptional activation of FMR1.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Glutamato Metabotrópico
/
Metilação de DNA
/
Proteína do X Frágil da Deficiência Intelectual
Tipo de estudo:
Clinical_trials
Limite:
Humans
/
Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article