@article{89a7e6724fb14334835b87cd6b94020a,
title = "GTPase Regulator Associated with Focal Adhesion Kinase 1 (GRAF1) Immunoglobulin-Associated Ataxia and Neuropathy",
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.",
keywords = "GTPase regulator, ataxia, neuropathy, tissue-based immunofluorescence, paraneoplastic, GRAF1",
author = "Pittock, {Sean J.} and Nora Alfugham and Kevin O'Connor and Shannon Hinson and Amy Kunchok and Lennon, {Vanda A.} and Lars Komorowski and Christian Probst and Andrew McKeon",
note = "Funding Information: We thank and acknowledge our research and administrative staff, Mary Curtis, and Jessica Sagen. Funding Information: Sean Pittock reports grants, personal fees, and nonfinancial support from Alexion Pharmaceuticals, Inc.; grants from Grifols, Autoimmune Encephalitis Alliance; grants, personal fees, nonfinancial support, and other from MedImmune, Inc.; consulting support from Astellas; and personal fees for consulting services from UCB Biopharma SRL. Dr. Pittock has patent 9,891,219 (Application 12–573,942) “Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an Individual That Is Aquaporin‐4 (AQP4)‐IgG Autoantibody Positive.” Dr. Pittock has patents pending for Kelch‐like Protein 11 (KLHL11), Septin 5, and Microtubule‐associated protein 1B (MAP1B) as markers of neurological autoimmunity and paraneoplastic disorders. Nora Alfugham, Kevin O'Connor, Amy Kunchok, and Shannon Hinson have nothing to disclose. Vanda A. Lennon receives royalties from Mayo Clinic licensing of diagnostic tests for Aquaporin‐4 (AQP4)‐IgG and is a named inventor on filed patents that relate to functional AQP4/Neuromyelitis opticaImmunoglobulin (NMO) ‐IgG assays and NMO‐IgG as a cancer marker. She has a patent pending for KLHL11, Septin 5, and MAP1B IgGs as markers of neurological autoimmunity and paraneoplastic disorders. Dr. Lennon receives royalties from RSR/Kronus for the sale of aquaporin‐4 antibody testing kits and for commercial aquaporin‐4 autoantibody testing performed outside Mayo Clinic and received research support from MN Partnership for Biotechnology and Medical Genomics. Lars Komorowski is an employee of the Euroimmun AG, a company that develops, produces, and manufactures immunoassays for the detection of disease‐associated antibodies. Christian Probst is an employee of the Euroimmun AG, a company that develops, produces, and manufactures immunoassays for the detection of disease‐associated antibodies. Andrew McKeon has patents pending for KLHL11, Septin 5, and MAP1B as markers of neurological autoimmunity and paraneoplastic disorders. He has consulted for Grifols, Medimmune, Euroimmun, Alexon (no personal compensation), and received research support from Medimmune, Euroimmun, Grifols, and Alexion. Funding Information: Mayo Clinic Foundation and Dr. O′Connor's fellowship funded by Euroimmun, AG. Publisher Copyright: {\textcopyright} 2020 International Parkinson and Movement Disorder Society",
year = "2020",
month = nov,
day = "1",
doi = "10.1002/mdc3.13036",
language = "English (US)",
volume = "7",
pages = "904--909",
journal = "Movement Disorders Clinical Practice",
issn = "2330-1619",
publisher = "John Wiley and Sons Ltd",
number = "8",
}