Acta Neuropathologica

, Volume 118, Issue 4, pp 561–573

Accumulation of TDP-43 and α-actin in an amyotrophic lateral sclerosis patient with the K17I ANG mutation

  • Danielle Seilhean
  • Cécile Cazeneuve
  • Valérie Thuriès
  • Odile Russaouen
  • Stéphanie Millecamps
  • François Salachas
  • Vincent Meininger
  • Eric LeGuern
  • Charles Duyckaerts
Case Report

Abstract

A K17I mutation in the ANG gene encoding angiogenin has been identified in a case that we previously published as ALS with neuronal intranuclear protein inclusions (Seilhean et al. in Acta Neuropathol 108:81–87, 2004). These inclusions were immunoreactive for smooth muscle α-actin but not for angiogenin. Moreover, they were not labeled by anti-TDP-43 antibodies, while numerous cytoplasmic inclusions immunoreactive for ubiquitin, p62 and TDP-43 were detected in both oligodendrocytes and neurons in various regions of the central nervous system. In addition, expression of smooth muscle α-actin was increased in the liver where severe steatosis was observed. This is the first neuropathological description of a case with an ANG mutation. Angiogenin is known to interact with actin. Like other proteins involved in ALS pathogenesis, such as senataxin, TDP-43 and FUS/TLS, it plays a role in RNA maturation.

Keywords

Neuropathology Motor neuron disease ALS Hippocampus Neuronal intranuclear inclusions Actin Angiogenin Actinin TDP-43 Steatosis 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Danielle Seilhean
    • 1
  • Cécile Cazeneuve
    • 2
  • Valérie Thuriès
    • 3
  • Odile Russaouen
    • 2
  • Stéphanie Millecamps
    • 4
  • François Salachas
    • 5
  • Vincent Meininger
    • 6
  • Eric LeGuern
    • 7
  • Charles Duyckaerts
    • 1
  1. 1.Département de NeuropathologieUPMC Université Paris 06, AP-HP, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, INSERM UMR-S 546 (DS) and UMR-S 679 (CD)Paris cedex 13France
  2. 2.Département de Génétique et CytogénétiqueAP-HP, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, U.F. de Neurogénétique Moléculaire et CellulaireParisFrance
  3. 3.Département de NeuropathologieAP-HP, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-SalpêtrièreParisFrance
  4. 4.Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus NeurodégénératifsCNRS UMR 7091, UPMC Université Paris 06, Groupe Hospitalier Pitié-SalpêtrièreParisFrance
  5. 5.AP-HP, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Fédération de Neurologie, Centre Référent Maladie Rares SLAParisFrance
  6. 6.UPMC Université Paris 06, AP-HP, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Fédération de Neurologie, Centre Référent Maladie Rares SLAParisFrance
  7. 7.Département de Génétique et CytogénétiqueUPMC Université Paris 06, INSERM, UMR-S 679 Neurologie and Thérapeutique Expérimentale, AP-HP, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, U.F. de Neurogénétique Moléculaire et CellulaireParisFrance

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