<b>Épissage alternatif, pathologie et thérapeutique moléculaire</b>

Corcos, Laurent; Solier, Stéphanie

doi:10.1051/medsci/2005213253

Cited by 6 publications

(4 citation statements)

References 48 publications

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“…This requires donor and acceptor sites splice [25]. The Splicing is catalysed by the "spliceosome", which consists of many proteins [26]. Among these include the splicing factor binding to family sequences cis regulatory: the amino acid-rich proteins serine and arginine, named SR proteins (rich serine) which consist of 50 to 300 amino acid residues.…”

Section: Discussionmentioning

confidence: 99%

Screening RB1 Gene in Algerian Patients and Predicting the Pathogenicity of Variations by In Silico Analysis

Boubkeur¹,

Louhibi²,

Abdi³

et al. 2017

J Clin Exp Ophthalmol

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Retinoblastoma is a pediatric retinal tumor initiated by biallelic inactivation of the retinoblastoma gene (RB1). Most of the alteration being unique and randomly distributed throughout the entire coding region. This study aimed firstly to identify mutations that may affect the RB1 gene in constitutional level witch contribute to the understanding of the molecular pathogenesis of this disease and for early detection of subject at risk and asymptomatic carriers. The detection of variations in 30 patient's DNAs was performed by high performance liquid chromatography (HPLC) followed by sequencing. Secondly, we developed a protocol in silico analysis using different software based on analytic methods (Align GVGD, Mutation tasting, SIFT, PolyPhen, I-Mutant and KD4V) and structural (Swiss-Pdb Viewer). This protocol was used to predict the deleterious effects of mutations on protein pRb. The spectrum of mutation included 2 missense mutations, 1 nonsense mutation, 1 deletion, 1 mutation affecting splice site and 2 polymorphisms. Among these mutations, some were identified in germinal level for children with no family history of the disease. Therefore, in silico analysis identified only three causal mutations, the first intronic mutation in the splice donor site caused probably a frame shift, giving rise to a truncated protein. The second missense mutation c.1903 G˃C was predicted to affect splicing processes. The third mutation c.1961T>A located in exon 20 may disrupt protein function and structure.In this study, in silico analysis has shown the effect of mutations on the structure and function of the protein. It is interesting to compare these results with others functional studies in order to evaluate the functionality of the mutations.

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Section: Discussionmentioning

confidence: 99%

Screening RB1 Gene in Algerian Patients and Predicting the Pathogenicity of Variations by In Silico Analysis

Boubkeur¹,

Louhibi²,

Abdi³

et al. 2017

J Clin Exp Ophthalmol

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“…De très nombreuses approches expé-rimentales ont fait la preuve de leur potentiel, tout particulièrement dans les maladies génétiques. Elles reposent sur des corrections d'épissages aberrants soit au moyen d'oligonucléotides modifiés, ou de molécules vectrices d'ARN normal (trans-épissage) [7] ou, plus largement, sur l'utilisation d'agents pharmacologiques dirigés contre certaines protéines du splicéosome. Ces agents inhibent l'épissage en général ou modulent spécifiquement l'épissage alternatif affectant ainsi un nombre réduit de gènes requis pour la progression du cancer.…”

Section: Abords Thérapeutiquesunclassified

L’épissage des ARN pré-messagers : quand le splicéosome perd pied

et al. 2016

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“…À l'inverse, l'utilisation de thérapies anti-angiogènes pour combattre le cancer a été proposée dès 1971 par Judah Folkman (1933Folkman ( -2008 [7]. Quelque trente ans plus tard, un anticorps humanisé capable de bloquer le VEGF (bevacizumab, Avastin ® , Genentech, États-Unis) est le premier agent antiangiogène accepté aux États-Unis par la Food and Drug Administration pour le traitement de cancers colorectaux en adjonction à la chimiothérapie [8].…”

Section: Nouvelleunclassified

“…Comme il ne semble pas indispensable à l'organisme, une thérapie ciblant spéci-fiquement le VEGF111 pourrait diminuer efficacement l'angiogenèse tumorale sans avoir les effets secondaires des traitements anti-VEGF actuels. Plusieurs stratégies sont envisageables : (1) inhibition de la liaison du VEGF111 aux récepteurs par des anticorps ou des aptamères spécifiques ; (2) inhibition spécifique de l'expression de VEGF111 par ARN interférentiel ; (3) inhibition du processus d'épissage impliqué dans la génération du VEGF111 ; La description de molécules capables de corriger l'épissage aberrant de certains gènes sans entraver l'épissage constitutif [8,9] laisse entrevoir de nouvelles solutions thérapeutiques. ‡ VEGF111: Dr Jekyll and Mr Hyde?…”

Section: Nouvelleunclassified