--- _id: '1916' abstract: - lang: eng text: 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. acknowledgement: Supported by the Deutsche Forschungsgemeinschaft (G.N.) article_processing_charge: No article_type: original author: - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Ali full_name: Fenstermaker, Ali last_name: Fenstermaker - first_name: Maha full_name: Zaki, Maha last_name: Zaki - first_name: Matan full_name: Hofree, Matan last_name: Hofree - first_name: Jennifer full_name: Silhavy, Jennifer last_name: Silhavy - first_name: Andrew full_name: Heiberg, Andrew last_name: Heiberg - first_name: Mostafa full_name: Abdellateef, Mostafa last_name: Abdellateef - first_name: Başak full_name: Rosti, Başak last_name: Rosti - first_name: Eric full_name: Scott, Eric last_name: Scott - first_name: Lobna full_name: Mansour, Lobna last_name: Mansour - first_name: Amira full_name: Masri, Amira last_name: Masri - first_name: Hülya full_name: Kayserili, Hülya last_name: Kayserili - first_name: Jumana full_name: Al Aama, Jumana last_name: Al Aama - first_name: Ghada full_name: Abdel Salam, Ghada last_name: Abdel Salam - first_name: Ariana full_name: Karminejad, Ariana last_name: Karminejad - first_name: Majdi full_name: Kara, Majdi last_name: Kara - first_name: Bülent full_name: Kara, Bülent last_name: Kara - first_name: Bita full_name: Bozorgmehri, Bita last_name: Bozorgmehri - first_name: Tawfeg full_name: Ben Omran, Tawfeg last_name: Ben Omran - first_name: Faezeh full_name: Mojahedi, Faezeh last_name: Mojahedi - first_name: Iman full_name: Mahmoud, Iman last_name: Mahmoud - first_name: Naïma full_name: Bouslam, Naïma last_name: Bouslam - first_name: Ahmed full_name: Bouhouche, Ahmed last_name: Bouhouche - first_name: Ali full_name: Benomar, Ali last_name: Benomar - first_name: Sylvain full_name: Hanein, Sylvain last_name: Hanein - first_name: Laure full_name: Raymond, Laure last_name: Raymond - first_name: Sylvie full_name: Forlani, Sylvie last_name: Forlani - first_name: Massimo full_name: Mascaro, Massimo last_name: Mascaro - first_name: Laila full_name: Selim, Laila last_name: Selim - first_name: Nabil full_name: Shehata, Nabil last_name: Shehata - first_name: Nasir full_name: Al Allawi, Nasir last_name: Al Allawi - first_name: Parayil full_name: Bindu, Parayil last_name: Bindu - first_name: Matloob full_name: Azam, Matloob last_name: Azam - first_name: Murat full_name: Günel, Murat last_name: Günel - first_name: Ahmet full_name: Caglayan, Ahmet last_name: Caglayan - first_name: Kaya full_name: Bilgüvar, Kaya last_name: Bilgüvar - first_name: Aslihan full_name: Tolun, Aslihan last_name: Tolun - first_name: Mahmoud full_name: Issa, Mahmoud last_name: Issa - first_name: Jana full_name: Schroth, Jana last_name: Schroth - first_name: Emily full_name: Spencer, Emily last_name: Spencer - first_name: Rasim full_name: Rosti, Rasim last_name: Rosti - first_name: Naiara full_name: Akizu, Naiara last_name: Akizu - first_name: Keith full_name: Vaux, Keith last_name: Vaux - first_name: Anide full_name: Johansen, Anide last_name: Johansen - first_name: Alice full_name: Koh, Alice last_name: Koh - first_name: Hisham full_name: Megahed, Hisham last_name: Megahed - first_name: Alexandra full_name: Dürr, Alexandra last_name: Dürr - first_name: Alexis full_name: Brice, Alexis last_name: Brice - first_name: Giovanni full_name: Stévanin, Giovanni last_name: Stévanin - first_name: Stacy full_name: Gabriel, Stacy last_name: Gabriel - first_name: Trey full_name: Ideker, Trey last_name: Ideker - first_name: Joseph full_name: Gleeson, Joseph last_name: Gleeson citation: ama: Novarino G, Fenstermaker A, Zaki M, et al. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 2014;343(6170):506-511. doi:10.1126/science.1247363 apa: Novarino, G., Fenstermaker, A., Zaki, M., Hofree, M., Silhavy, J., Heiberg, A., … Gleeson, J. (2014). Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1247363 chicago: Novarino, Gaia, Ali Fenstermaker, Maha Zaki, Matan Hofree, Jennifer Silhavy, Andrew Heiberg, Mostafa Abdellateef, et al. “Exome Sequencing Links Corticospinal Motor Neuron Disease to Common Neurodegenerative Disorders.” Science. American Association for the Advancement of Science, 2014. https://doi.org/10.1126/science.1247363. ieee: G. Novarino et al., “Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders,” Science, vol. 343, no. 6170. American Association for the Advancement of Science, pp. 506–511, 2014. ista: Novarino G, Fenstermaker A, Zaki M, Hofree M, Silhavy J, Heiberg A, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al Aama J, Abdel Salam G, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben Omran T, Mojahedi F, Mahmoud I, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al Allawi N, Bindu P, Azam M, Günel M, Caglayan A, Bilgüvar K, Tolun A, Issa M, Schroth J, Spencer E, Rosti R, Akizu N, Vaux K, Johansen A, Koh A, Megahed H, Dürr A, Brice A, Stévanin G, Gabriel S, Ideker T, Gleeson J. 2014. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 343(6170), 506–511. mla: Novarino, Gaia, et al. “Exome Sequencing Links Corticospinal Motor Neuron Disease to Common Neurodegenerative Disorders.” Science, vol. 343, no. 6170, American Association for the Advancement of Science, 2014, pp. 506–11, doi:10.1126/science.1247363. short: G. Novarino, A. Fenstermaker, M. Zaki, M. Hofree, J. Silhavy, A. Heiberg, M. Abdellateef, B. Rosti, E. Scott, L. Mansour, A. Masri, H. Kayserili, J. Al Aama, G. Abdel Salam, A. Karminejad, M. Kara, B. Kara, B. Bozorgmehri, T. Ben Omran, F. Mojahedi, I. Mahmoud, N. Bouslam, A. Bouhouche, A. Benomar, S. Hanein, L. Raymond, S. Forlani, M. Mascaro, L. Selim, N. Shehata, N. Al Allawi, P. Bindu, M. Azam, M. Günel, A. Caglayan, K. Bilgüvar, A. Tolun, M. Issa, J. Schroth, E. Spencer, R. Rosti, N. Akizu, K. Vaux, A. Johansen, A. Koh, H. Megahed, A. Dürr, A. Brice, G. Stévanin, S. Gabriel, T. Ideker, J. Gleeson, Science 343 (2014) 506–511. date_created: 2018-12-11T11:54:42Z date_published: 2014-01-31T00:00:00Z date_updated: 2021-01-12T06:54:03Z day: '31' department: - _id: GaNo doi: 10.1126/science.1247363 external_id: pmid: - '24482476' intvolume: ' 343' issue: '6170' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157572/ month: '01' oa: 1 oa_version: Submitted Version page: 506 - 511 pmid: 1 publication: Science publication_status: published publisher: American Association for the Advancement of Science publist_id: '5178' quality_controlled: '1' scopus_import: 1 status: public title: Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 343 year: '2014' ...