Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to characterise a novel family with very slowly progressive pure spinocerebellar ataxia (SCA) caused by a deletion in the inositol 1,4,5-triphosphate receptor 1 (ITPR1) gene on chromosome 3. This is a detailed clinical, genetic, and radiological description of the genotype. Deletions in ITPR1 have been shown to cause SCA15/SCA16 in six families to date. A further Japanese family has been identified with an ITPR1 point mutation. The exact prevalence is as yet unknown, but is probably higher than previously thought. The clinical phenotype of the family is described, and videotaped clinical examinations are presented. Serial brain magnetic resonance imaging studies were carried out on one affected individual, and genetic analysis was performed on several family members. Protein analysis confirmed the ITPR1 deletion. Affected subjects display a remarkably slow, almost pure cerebellar syndrome. Serial magnetic resonance imaging shows moderate cerebellar atrophy with mild inferior parietal and temporal cortical volume loss. Genetic analysis shows a deletion of 346,487 bp in ITPR1 (the second largest ITPR1 deletion reported to date), suggesting SCA15 is due to a loss of ITPR1 function. Western blotting of lymphoblastoid cell line protein confirms reduced ITPR1 protein levels. SCA15 is a slowly or nonprogressive pure cerebellar ataxia, which appears to be caused by a loss of ITPR1 function and a reduction in the translated protein. Patients with nonprogressive or slowly progressive ataxia should be screened for ITPR1 defects.
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PMID:An ITPR1 gene deletion causes spinocerebellar ataxia 15/16: a genetic, clinical and radiological description. 2066 19

We report on a serum autoantibody associated with cerebellar ataxia. Immunohistochemical studies of sera from four patients referred for autoantibody testing revealed binding of high-titer (up to 1:5,000) IgG antibodies, mainly IgG1, to the molecular layer, Purkinje cell layer, and white matter on mouse, rat, porcine, and monkey cerebellum sections. The antibody bound to PC somata, dendrites, and axons, resulting in a binding pattern similar to that reported for anti-Ca/anti-ARHGAP26, but did not react with recombinant ARHGAP26. Extensive control studies were performed to rule out a broad panel of previously described paraneoplastic and non-paraneoplastic anti-neural autoantibodies. The characteristic binding pattern as well as double staining experiments suggested inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) as the target antigen. Verification of the antigen included specific neutralization of the tissue reaction following preadsorption with ITPR1 (but not ARHGAP26) and a dot-blot assay with purified ITPR1 protein. By contrast, anti-ARHGAP26-positive sera did not bind to ITPR1. In a parallel approach, a combination of histoimmunoprecipitation and mass spectrometry also identified ITPR1 as the target antigen. Finally, a recombinant cell-based immunofluorescence assay using HEK293 cells expressing ITPR1 and ARHGAP26, respectively, confirmed the identification of ITPR1. Mutations of ITPR1 have previously been implicated in spinocerebellar ataxia with and without cognitive decline. Our findings suggest a role of autoimmunity against ITPR1 in the pathogenesis of autoimmune cerebellitis and extend the panel of diagnostic markers for this disease.
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PMID:Antibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in cerebellar ataxia. 2549 30