---
_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'
...