Identificação e estudo funcional de genes associados com doenças neurológicas / Identification an functional estudy of genes associated with neurological diseases

AUTOR(ES)

Gustavo de Alencastro

DATA DE PUBLICAÇÃO

2008

RESUMO

In this work we have used different approaches to the study of genes associated with CNS development and function as well as with neurological diseases: 1) one study involved the identification of the allele associated with an X-linked recessive sindromic form of mental retardation, Snyder-Robinson syndrome, in a Brazilian family. Using genetic linkage analysis and candidate gene strategy, we identified the second pathogenic mutation in the SMS gene (that encodes the spermine synthase enzyme) associated with the Snyder-Robinson syndrome. The identification of this mutation contributed to: the delineation and expansion of the clinical spectrum of the syndrome, highlight important domains for spermine synthase protein functioning, demonstrate the importance of this protein in cognitive processes, and also a precise genetic counseling for family members; 2) a second study involved the mutation screening of ARHGEF9, gene encoding the collybistin protein, which is involved in inhibitory synaptogenesis, in Brazilian patients with hyperekplexia (6 patients) and in patients with mental retardation associated with epilepsy (22 patients). We did not identify any pathogenic alteration in the ARHGEF9, gene in the 28 studied patients, but the number of patients analysed was very small. However, the possibility remains that additional mutations in ARHGEF9, may contribute to other cases of hyperekplexia and mental retardation associated with epilepsy; 3) the last study involved the functional analysis of collybistin protein. In order to identify other proteins that interact with human collybistin, we used the yeast two-hybrid system and in vitro e in vivo co-immunoprecipitation experiments. We identified the eIF3-p40 protein as collybistin and gephyrin (another protein involved in the function of inhibitory synapses that also interacts with collybistin) binding partner. The eIF3-p40 protein is one of the subunits of the eukaryotic initiation factor 3 complex (eIF3). These interactions link the collybistin and gephyrin proteins to the protein translation machinery, revealing a putative new role of these proteins in the translation control at inhibitory postsynaptic sites.

ASSUNTO(S)

retardo mental ligado ao cromossomo x x-linked mental retardation collybistin (arhgef9gene) neurological diseases colibistina (gene arhgef9 ) doenças neurológicas

Documentos Relacionados

• Functional identification and genomic structure of Paracoccidioides brasiliensis nuclear genes associated to cytochrome c oxidase activity.
• Multimorbidade e desfechos associados entre idosos hospitalizados com doenças neurológicas
• A maternidade em mães de crianças com doenças neurológicas crônicas: um estudo sobre a sobrecarga e a qualidade de vida
• Identificação de genes de Burkholderia sp. associados ao controle biológico de Pectobacterium carotovora.
• Identification and functional analysis of signal transduction-related genes in sugarcane.