Retards mentaux liés au chromosome X.

Abstract

Grâce à des efforts concertés entre cliniciens, généticiens et biologistes, les bases génétiques et moléculaires des retards mentaux liés au chromosome X commencent à être élucidées. Outre les retombées et les perspectives médico-sociales, ces progrès très significatifs offrent la possibilité d’étudier les bases cellulaires de certaines formes de retards mentaux non spécifiques et de les conceptualiser. En effet, sur la base des données actuelles, il est raisonnable de penser que les déficits cognitifs associés aux dysfonctionnements de certains gènes seraient dus à des perturbations de l’organisation du cytosquelette cellulaire. En effet, le rôle crucial du cytosquelette dans la croissance des neurites ainsi que dans la plasticité synaptique et neuronale est devenu une donnée incontestable.

Alhough the genetic causes of X-linked mental retardation (XLMR) are heterogenous and complex, recent concerted efforts between physicians and biologists allowed to overcome major difficulties in the identification of a number of genes involved in these diseases. Over the past two years, significant progress was made in the understanding of the molecular basis underlying both XLMR, which can be distinguished by specific phenotypic or genenetic markers ('syndromal' forms of XLMR), and MRX, or nonspecific (or idiopathic) mental retardation. Major breakthroughs include the discovery that the genes responsible for these conditions encode proteins involved in signaling pathways regulating cytoskeleton organization, synaptic vesicular transport, and maybe other cellular functions. These data also suggest a provocative picture in which MRX can be regarded as disorders resulting from defects in genes required for processes such as the remodeling, establishment, stabilization of connections between neuronal cells. Such processes are crucial for the development of intellectual and cognitive functions. As these functions evolve mainly in post-natal stages through contact with various types of stimulus and environments, a potential therapeutic approach could be based on the development of drugs that target cellular signaling pathways shown to be implicated in MRX. [References: 37]