Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.

Journal: Science (New York, N.Y.)

Volume: 343

Issue: 6170

Year of Publication: 2014

Affiliated Institutions:  Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA , USA. Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Center, Cairo , Egypt. Department of Computer Science and Engineering and Department of Medicine, University of California, San Diego, La Jolla, CA , USA. Department of Pediatric Neurology, Neurometabolic Unit, Cairo University Children's Hospital, Cairo , Egypt. Division of Child Neurology, Department of Pediatrics, University of Jordan, Amman , Jordan. Istanbul University, Istanbul Medical Faculty, Medical Genetics Department, Istanbul, Turkey. Department of Genetic Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran. Department of Pediatrics, Tripoli Children's Hospital, Tripoli, Libya. Kocaeli University, Medical Faculty, Department of Pediatric Neurology, Umuttepe, Kocaeli, Turkey. Clinical and Metabolic Genetics Division, Department of Pediatrics, Hamad Medical Corporation, Doha , Qatar. Mashhad Medical Genetic Counseling Center, Mashhad, Iran. Université Mohammed V Souissi, Equipe de Recherchéde Maladies Neurodégéneratives (ERMN) and Centre de Recherche en Épidémiologie Clinique et Essais Thérapeutiques (CRECET), Rabat, Morocco. Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U, CNRS UMR; UPMC Univ Paris VI UMR_S, Paris, France. Department of Pediatrics and Neonatology, Saudi German Hospital, Post Office Box , Riyadh, Kingdom of Saudi Arabia. Department of Pathology, School of Medicine, University of Dohuk, Dohuk, Iraq. Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. Department of Pediatrics and Child Neurology, Wah Medical College, Wah Cantt, Pakistan. Department of Genetics and Neurosurgery, Yale University School of Medicine, New Haven, CT , USA. Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey. Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA , USA.

Abstract summary 

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.

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

Study Outcome 

Source Link: Visit source

Statistics
Citations :  Blackstone C. Annu. Rev. Neurosci. 2012;35:25–47.
Authors :  52
Identifiers
Doi : 10.1126/science.1247363
SSN : 1095-9203
Study Population
Male,Female
Mesh Terms
Animals
Other Terms
Study Design
Study Approach
Country of Study
Publication Country
United States