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Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.
Novarino, Gaia; Fenstermaker, Ali G; Zaki, Maha S; Hofree, Matan; Silhavy, Jennifer L; Heiberg, Andrew D; Abdellateef, Mostafa; Rosti, Basak; Scott, Eric; Mansour, Lobna; Masri, Amira; Kayserili, Hulya; Al-Aama, Jumana Y; Abdel-Salam, Ghada M H; Karminejad, Ariana; Kara, Majdi; Kara, Bulent; Bozorgmehri, Bita; Ben-Omran, Tawfeg; Mojahedi, Faezeh; El Din Mahmoud, Iman Gamal; Bouslam, Naima; Bouhouche, Ahmed; Benomar, Ali; Hanein, Sylvain; Raymond, Laure; Forlani, Sylvie; Mascaro, Massimo; Selim, Laila; Shehata, Nabil; Al-Allawi, Nasir; Bindu, P S; Azam, Matloob; Gunel, Murat; Caglayan, Ahmet; Bilguvar, Kaya; Tolun, Aslihan; Issa, Mahmoud Y; Schroth, Jana; Spencer, Emily G; Rosti, Rasim O; Akizu, Naiara; Vaux, Keith K; Johansen, Anide; Koh, Alice A; Megahed, Hisham; Durr, Alexandra; Brice, Alexis; Stevanin, Giovanni; Gabriel, Stacy B.
Afiliación
  • Novarino G; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Fenstermaker AG; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Zaki MS; Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Center, Cairo 12311, Egypt.
  • Hofree M; Department of Computer Science and Engineering and Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Silhavy JL; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Heiberg AD; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Abdellateef M; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Rosti B; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Scott E; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Mansour L; Department of Pediatric Neurology, Neurometabolic Unit, Cairo University Children's Hospital, Cairo 406, Egypt.
  • Masri A; Division of Child Neurology, Department of Pediatrics, University of Jordan, Amman 11942, Jordan.
  • Kayserili H; Istanbul University, Istanbul Medical Faculty, Medical Genetics Department, 34093 Istanbul, Turkey.
  • Al-Aama JY; Department of Genetic Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
  • Abdel-Salam GMH; Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Center, Cairo 12311, Egypt.
  • Karminejad A; Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
  • Kara M; Department of Pediatrics, Tripoli Children's Hospital, Tripoli, Libya.
  • Kara B; Kocaeli University, Medical Faculty, Department of Pediatric Neurology, 41380 Umuttepe, Kocaeli, Turkey.
  • Bozorgmehri B; Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
  • Ben-Omran T; Clinical and Metabolic Genetics Division, Department of Pediatrics, Hamad Medical Corporation, Doha 3050, Qatar.
  • Mojahedi F; Mashhad Medical Genetic Counseling Center, 91767 Mashhad, Iran.
  • El Din Mahmoud IG; Department of Pediatric Neurology, Neurometabolic Unit, Cairo University Children's Hospital, Cairo 406, Egypt.
  • Bouslam N; Université Mohammed V Souissi, Equipe de Recherchéde Maladies Neurodégéneratives (ERMN) and Centre de Recherche en Épidémiologie Clinique et Essais Thérapeutiques (CRECET), 6402 Rabat, Morocco.
  • Bouhouche A; Université Mohammed V Souissi, Equipe de Recherchéde Maladies Neurodégéneratives (ERMN) and Centre de Recherche en Épidémiologie Clinique et Essais Thérapeutiques (CRECET), 6402 Rabat, Morocco.
  • Benomar A; Université Mohammed V Souissi, Equipe de Recherchéde Maladies Neurodégéneratives (ERMN) and Centre de Recherche en Épidémiologie Clinique et Essais Thérapeutiques (CRECET), 6402 Rabat, Morocco.
  • Hanein S; Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225; UPMC Univ Paris VI UMR_S975, 75013 Paris, France.
  • Raymond L; Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225; UPMC Univ Paris VI UMR_S975, 75013 Paris, France.
  • Forlani S; Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225; UPMC Univ Paris VI UMR_S975, 75013 Paris, France.
  • Mascaro M; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Selim L; Department of Pediatric Neurology, Neurometabolic Unit, Cairo University Children's Hospital, Cairo 406, Egypt.
  • Shehata N; Department of Pediatrics and Neonatology, Saudi German Hospital, Post Office Box 84348, Riyadh, Kingdom of Saudi Arabia.
  • Al-Allawi N; Department of Pathology, School of Medicine, University of Dohuk, Dohuk, Iraq.
  • Bindu PS; Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India.
  • Azam M; Department of Pediatrics and Child Neurology, Wah Medical College, Wah Cantt, Pakistan.
  • Gunel M; Department of Genetics and Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Caglayan A; Department of Genetics and Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Bilguvar K; Department of Genetics and Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Tolun A; Department of Molecular Biology and Genetics, Bogazici University, 34342 Istanbul, Turkey.
  • Issa MY; Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Center, Cairo 12311, Egypt.
  • Schroth J; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Spencer EG; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Rosti RO; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Akizu N; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Vaux KK; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Johansen A; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Koh AA; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
  • Megahed H; Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Center, Cairo 12311, Egypt.
  • Durr A; Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225; UPMC Univ Paris VI UMR_S975, 75013 Paris, France.
  • Brice A; Assistance Publique-Hôpitaux de Paris, Fédération de Génétique, Pitié-Salpêtrière Hospital, 75013 Paris, France.
  • Stevanin G; Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225; UPMC Univ Paris VI UMR_S975, 75013 Paris, France.
  • Gabriel SB; Assistance Publique-Hôpitaux de Paris, Fédération de Génétique, Pitié-Salpêtrière Hospital, 75013 Paris, France.
Science ; 343(6170): 506-511, 2014 Jan 31.
Article en En | MEDLINE | ID: mdl-24482476
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.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Tractos Piramidales / Paraplejía Espástica Hereditaria / Enfermedad de la Neurona Motora / Estudios de Asociación Genética / Exoma / Neuronas Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Science Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Tractos Piramidales / Paraplejía Espástica Hereditaria / Enfermedad de la Neurona Motora / Estudios de Asociación Genética / Exoma / Neuronas Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Science Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos