Identification of 18 new causative genes in hereditary spastic paraplegias

Three members of the SPATAX network (Cairo, Rabat and Paris), including a EPHE research team of the ICM institute, took part to an international study leaded by Joseph Gleeson (San Diego) identifying 18 new genes implicated in hereditary spastic paraplegias (HSP). This work, published on January the 31th on the prestigious website of the journal Science, arises from a worldwide collaboration and strongly contributes to the understanding of the genetic origin of HSP, a prerequisite to future therapies, and to future identification of new causative genes.

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REFERENCE (Members of the SPATAX network in bold): Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, Heiberg AD, Abdellatef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al-Aama JY, Abdel-Salam GMH, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben-Omran T, Mojahedi F, El Din Mahmoud IG, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al-Allawi N, Bindu PS, Azam M, Gunel M, Caglayan A, Bilguvar K, Tolun A, Issa MY, Schroth J, Spencer EG, Rosti RO, Akizu N, Vaux KK, Johansen A, Koh AA, Megahed H, Durr A, Brice A, Stevanin G, Gabriel SB, Ideker T, Gleeson JG. Exome Sequencing Links Corticospinal Motor Neuron Disease to Common Neurodegenerative Disorders. Science 2014, 343:506-511.

ABSTRACT: Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease.

LINK to the manuscript : http://www.sciencemag.org/content/343/6170/506.abstract

 

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