Clinicopathologic report of ocular involvement in ALS patients with C9orf72 mutation

Amani A. Fawzi*, Joseph M. Simonett, Patryk Purta, Heather E. Moss, Jessica L. Lowry, Han Xiang Deng, Nailah Siddique, Robert Sufit, Eileen H. Bigio, Nicholas J. Volpe, Teepu Siddique

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Our objective was to present clinicopathologic evidence of anterior visual pathway involvement in patients with amyotrophic lateral sclerosis (ALS) secondary to a C9orf72 mutation. Two related patients from an extended pedigree with ALS and GGGGCC hexanucleotide repeat expansion in the C9orf72 gene (C9-ALS) underwent neuro-ophthalmologic examination. Following death and tissue donation of the younger ALS patient, histopathologic examination of the retina, optic nerve and central nervous system (CNS) was performed. Ophthalmologic examination revealed contrast sensitivity impairment in the younger C9-ALS patient. Immunohistochemistry performed on this patient's donor tissue demonstrated p62-positive, pTDP43-negative perinuclear inclusions in the inner nuclear layer of the retina and CNS. Further colocalization with GLT-1 and recoverin suggested that the majority of retinal p62-positive inclusions are found within cone bipolar cells as well as some amacrine and horizontal cells. In conclusion, this is the first report that identifies disease-specific pathologic inclusions in the anterior visual pathway of a patient with a C9orf72 mutation. Cone bipolar cell involvement within the inner nuclear layer of the retina may explain the observed subtle visual function deficiencies in this patient. Further clinical and histopathologic studies are needed to fully characterize a larger population of C9-ALS patients and explore these findings in other forms of ALS.

Original languageEnglish (US)
Pages (from-to)569-580
Number of pages12
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Issue number7-8
StatePublished - Dec 1 2014


  • Amyotrophic lateral sclerosis
  • C9orf72
  • Midget bipolar cells
  • Neuropathology
  • Pathology
  • Retina
  • Ubiquitin

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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