GTPase Regulator Associated with Focal Adhesion Kinase 1 (GRAF1) Immunoglobulin-Associated Ataxia and Neuropathy

Sean J. Pittock, Nora Alfugham, Kevin O'Connor, Shannon Hinson, Amy Kunchok, Vanda A. Lennon, Lars Komorowski, Christian Probst, Andrew McKeon

Research output: Contribution to journalArticlepeer-review

Abstract

Background: To date, 10 patients with GTPase Regulator Associated with Focal Adhesion Kinase 1/Rho GTPase Activating Protein 26-Immunoglobulin (GRAF1/ARHGAP26-IgG) associated neurological disorders have been described, most with ataxia. Objective: To report the clinical, oncological, and radiological associations of GRAF1 autoantibodies. Methods: We identified 17 patients whose serum and/or cerebrospinal fluid IgG was confirmed to target GRAF1/ARHGAP26-IgG by both tissue-based immunofluorescence and transfected cell-based assay. Clinical information was available on 14 patients. Results: The median age at neurological symptom onset was 51 years, and 8 (47%) were men. The predominant clinical features were subacute progressive cerebellar ataxia (13) or peripheral neuropathy (2). Magnetic resonance imaging brain (7 available) showed cerebellar atrophy (4, 1 also cerebrum and brainstem atrophy). Of 7 cerebrospinal fluids available for testing, 5 showed pleocytosis with oligoclonal bands in 3. Squamous cell carcinoma was observed in 3 patients (head and neck [2], lung [1]). Conclusion: GTPase Regulator Associated with Focal Adhesion Kinase 1 autoimmunity manifests commonly with subacute ataxia and cerebellar degeneration with a potential association with squamous cell carcinoma. Peripheral neuropathy may also be encountered. Cases in this series responded poorly to immunotherapy.

Original languageEnglish (US)
Pages (from-to)904-909
Number of pages6
JournalMovement Disorders Clinical Practice
Volume7
Issue number8
DOIs
StatePublished - Nov 1 2020

Keywords

  • GTPase regulator, ataxia, neuropathy, tissue-based immunofluorescence, paraneoplastic, GRAF1

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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