Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders

Gaia Novarino; Ali G. Fenstermaker; Maha S. Zaki; Matan Hofree; Jennifer L. Silhavy; Andrew D. Heiberg; Mostafa Abdellateef; Basak Rosti; Eric Scott; Lobna Mansour; Amira Masri; Hulya Kayserili; Jumana Y. Al-Aama; Ghada M.H. Abdel-Salam; Ariana Karminejad; Majdi Kara; Bulent Kara; Bita Bozorgmehri; Tawfeg Ben-Omran; Faezeh Mojahedi; Iman Gamal El Din Mahmoud; Naima Bouslam; Ahmed Bouhouche; Ali Benomar; Sylvain Hanein; Laure Raymond; Sylvie Forlani; Massimo Mascaro; Laila Selim; Nabil Shehata; Nasir Al-Allawi; P. S. Bindu; Matloob Azam; Murat Gunel; Ahmet Caglayan; Kaya Bilguvar; Aslihan Tolun; Mahmoud Y. Issa; Jana Schroth; Emily G. Spencer; Rasim O. Rosti; Naiara Akizu; Keith K. Vaux; Anide Johansen; Alice A. Koh; Hisham Megahed; Alexandra Durr; Alexis Brice; Giovanni Stevanin; Stacy B. Gabriel; Trey Ideker; Joseph G. Gleeson

doi:10.1126/science.1247363

Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders

Gaia Novarino, Ali G. Fenstermaker, Maha S. Zaki, Matan Hofree, Jennifer L. Silhavy, Andrew D. Heiberg, Mostafa Abdellateef, Basak Rosti, Eric Scott, Lobna Mansour, Amira Masri, Hulya Kayserili, Jumana Y. Al-Aama, Ghada M.H. Abdel-Salam, Ariana Karminejad, Majdi Kara, Bulent Kara, Bita Bozorgmehri, Tawfeg Ben-Omran, Faezeh MojahediIman Gamal El Din Mahmoud, Naima Bouslam, Ahmed Bouhouche, Ali Benomar, Sylvain Hanein, Laure Raymond, Sylvie Forlani, Massimo Mascaro, Laila Selim, Nabil Shehata, Nasir Al-Allawi, P. S. Bindu, Matloob Azam, Murat Gunel, Ahmet Caglayan, Kaya Bilguvar, Aslihan Tolun, Mahmoud Y. Issa, Jana Schroth, Emily G. Spencer, Rasim O. Rosti, Naiara Akizu, Keith K. Vaux, Anide Johansen, Alice A. Koh, Hisham Megahed, Alexandra Durr, Alexis Brice, Giovanni Stevanin, Stacy B. Gabriel, Trey Ideker, Joseph G. Gleeson^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

419 Scopus citations

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.

Original language	English
Pages (from-to)	506-511
Number of pages	6
Journal	Science
Volume	343
Issue number	6170
DOIs	https://doi.org/10.1126/science.1247363
State	Published - 2014
Externally published	Yes

Access to Document

10.1126/science.1247363

Cite this

Novarino, G., Fenstermaker, A. G., Zaki, M. S., Hofree, M., Silhavy, J. L., Heiberg, A. D., Abdellateef, M., Rosti, B., Scott, E., Mansour, L., Masri, A., Kayserili, H., Al-Aama, J. Y., Abdel-Salam, G. M. H., Karminejad, A., Kara, M., Kara, B., Bozorgmehri, B., Ben-Omran, T., ... Gleeson, J. G. (2014). Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science, 343(6170), 506-511. https://doi.org/10.1126/science.1247363

@article{bfac80533d6840dfae9e8132c7f66b58,

title = "Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders",

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.",

author = "Gaia Novarino and Fenstermaker, {Ali G.} and Zaki, {Maha S.} and Matan Hofree and Silhavy, {Jennifer L.} and Heiberg, {Andrew D.} and Mostafa Abdellateef and Basak Rosti and Eric Scott and Lobna Mansour and Amira Masri and Hulya Kayserili and Al-Aama, {Jumana Y.} and Abdel-Salam, {Ghada M.H.} and Ariana Karminejad and Majdi Kara and Bulent Kara and Bita Bozorgmehri and Tawfeg Ben-Omran and Faezeh Mojahedi and Mahmoud, {Iman Gamal El Din} and Naima Bouslam and Ahmed Bouhouche and Ali Benomar and Sylvain Hanein and Laure Raymond and Sylvie Forlani and Massimo Mascaro and Laila Selim and Nabil Shehata and Nasir Al-Allawi and Bindu, {P. S.} and Matloob Azam and Murat Gunel and Ahmet Caglayan and Kaya Bilguvar and Aslihan Tolun and Issa, {Mahmoud Y.} and Jana Schroth and Spencer, {Emily G.} and Rosti, {Rasim O.} and Naiara Akizu and Vaux, {Keith K.} and Anide Johansen and Koh, {Alice A.} and Hisham Megahed and Alexandra Durr and Alexis Brice and Giovanni Stevanin and Gabriel, {Stacy B.} and Trey Ideker and Gleeson, {Joseph G.}",

year = "2014",

doi = "10.1126/science.1247363",

language = "אנגלית",

volume = "343",

pages = "506--511",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6170",

}

Novarino, G, Fenstermaker, AG, Zaki, MS, Hofree, M, Silhavy, JL, Heiberg, AD, Abdellateef, 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, Mahmoud, IGED, 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 2014, 'Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders', Science, vol. 343, no. 6170, pp. 506-511. https://doi.org/10.1126/science.1247363

TY - JOUR

T1 - Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders

AU - Novarino, Gaia

AU - Fenstermaker, Ali G.

AU - Zaki, Maha S.

AU - Hofree, Matan

AU - Silhavy, Jennifer L.

AU - Heiberg, Andrew D.

AU - Abdellateef, Mostafa

AU - Rosti, Basak

AU - Scott, Eric

AU - Mansour, Lobna

AU - Masri, Amira

AU - Kayserili, Hulya

AU - Al-Aama, Jumana Y.

AU - Abdel-Salam, Ghada M.H.

AU - Karminejad, Ariana

AU - Kara, Majdi

AU - Kara, Bulent

AU - Bozorgmehri, Bita

AU - Ben-Omran, Tawfeg

AU - Mojahedi, Faezeh

AU - Mahmoud, Iman Gamal El Din

AU - Bouslam, Naima

AU - Bouhouche, Ahmed

AU - Benomar, Ali

AU - Hanein, Sylvain

AU - Raymond, Laure

AU - Forlani, Sylvie

AU - Mascaro, Massimo

AU - Selim, Laila

AU - Shehata, Nabil

AU - Al-Allawi, Nasir

AU - Bindu, P. S.

AU - Azam, Matloob

AU - Gunel, Murat

AU - Caglayan, Ahmet

AU - Bilguvar, Kaya

AU - Tolun, Aslihan

AU - Issa, Mahmoud Y.

AU - Schroth, Jana

AU - Spencer, Emily G.

AU - Rosti, Rasim O.

AU - Akizu, Naiara

AU - Vaux, Keith K.

AU - Johansen, Anide

AU - Koh, Alice A.

AU - Megahed, Hisham

AU - Durr, Alexandra

AU - Brice, Alexis

AU - Stevanin, Giovanni

AU - Gabriel, Stacy B.

AU - Ideker, Trey

AU - Gleeson, Joseph G.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84893041011&partnerID=8YFLogxK

U2 - 10.1126/science.1247363

DO - 10.1126/science.1247363

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

AN - SCOPUS:84893041011

SN - 0036-8075

VL - 343

SP - 506

EP - 511

JO - Science

JF - Science

IS - 6170

ER -

Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders

Abstract

Access to Document

Other files and links

Fingerprint

Cite this