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An association of Myelin Oligodendrocyte Glycoprotein (MOG) gene variants with white matter volume in pediatric obsessive-compulsive disorder.

ABSTRACT: An increasing number of neuroimaging studies have implicated alterations of white matter in obsessive-compulsive disorder (OCD). The myelin oligodendrocyte glycoprotein (MOG) gene plays a major role in myelination, and has previously demonstrated significant association with this disorder, thus variations in this gene may contribute to observed white matter alterations. The purpose of this study is to examine the relationship between white matter volume in OCD and genetic variations in the MOG gene. Two polymorphisms in the MOG gene, MOG(C1334T) and MOG(C10991T), were investigated for association with total white matter volume as measured using volumetric magnetic resonance imaging in 37 pediatric OCD patients. We compared white matter volumes between allele and genotype groups for each polymorphism using ANCOVA. A significant relationship was detected between genotype C/C of MOG(C10991T) and decreased total white matter volume (P = 0.016). Our results showed an association between a MOG genetic variant and white matter volume. This finding is intriguing in light of the posited role of white matter alteration in the etiology of at least some cases of childhood-onset OCD. Further investigation with larger samples and sub-regional white matter volume phenotypes is warranted.

SUBMITTER: Zai G

PROVIDER: S-EPMC7775903 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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An association of Myelin Oligodendrocyte Glycoprotein (MOG) gene variants with white matter volume in pediatric obsessive-compulsive disorder.

Zai Gwyneth G Arnold Paul D PD Richter Margaret A MA Hanna Gregory L GL Rosenberg David D Kennedy James L JL

Psychiatry research. Neuroimaging 20201121

An increasing number of neuroimaging studies have implicated alterations of white matter in obsessive-compulsive disorder (OCD). The myelin oligodendrocyte glycoprotein (MOG) gene plays a major role in myelination, and has previously demonstrated significant association with this disorder, thus variations in this gene may contribute to observed white matter alterations. The purpose of this study is to examine the relationship between white matter volume in OCD and genetic variations in the MOG g ...[more]

PMID: 33302097

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Project description:Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease is a recently described central nervous system (CNS) inflammatory disorder with phenotypic overlap with Neuromyelitis Optica Spectrum Disorder (NMOSD). NMOSD seronegative patients, and those with limited forms of the disorder, become suspects for MOG antibody-associated disease. We describe a multi-ethnic population with MOG antibody seropositivity from the University of British Columbia MS/NMO clinic. Methods: AQP4-antibody seronegative patients presenting 2005-2016 with CNS inflammatory disease suspicious for NMOSD, as well as 20 MS controls, were retrospectively tested for MOG-IgG1 antibodies by live cell-based assay at Oxford Autoimmune Neurology Diagnostic Laboratory (UK) and by a commercial fixed cell-based assay at MitogenDx (Calgary, Canada). Additional MOG seropositive cases were identified through routine clinical interaction (2016-2018) using one of these laboratories. Clinical data was reviewed retrospectively. Results: Retrospective testing identified 21 MOG seropositives (14 by live assay only, 3 by fixed assay only and 4 by both) representing 14% of the "NMOSD suspects" cohort. One multiple sclerosis (MS) control serum was MOG seropositive. Twenty additional MOG positive cases were identified prospectively. Of 42 patients (27 female), median disease onset age was 29 years (range 3-62; 9 pediatric cases), 20 (47%) were non-Caucasian, and 3 (7%) had comorbid autoimmune disease. Most common onset phenotypes were optic neuritis (23, 55%; 8 bilateral) and myelitis (9, 21%; 6 longitudinally extensive) Three of the patients in our cohort experienced cortical encephalitis; two presented with seizures. Onset was moderate-severe in 64%, but 74% had good response to initial steroid therapy. Cumulative relapse probability for the MOG positive group at 1 year was 0.428 and at 4 years was 0.628. Most had abnormal brain imaging, including cortical encephalitis and poorly demarcated subcortical and infratentorial lesions. Few "classic MS" lesions were seen. Optic nerve lesions (frequently bilateral) were long and predominantly anterior, but 5 extended to the chiasm. Spinal cord lesions were long and short, with involvement of multiple spinal regions simultaneously, including the conus medullaris. Conclusions: Our MOG seropositive patients display phenotypes similar to previous descriptions, including cortical lesions with seizures and conus medullaris involvement. Many patients relapsed, predominantly in a different CNS location from onset. Serologic data from two different cell-based antibody assays highlight the discrepancies between live and fixed testing for MOG antibodies.

Project description:BackgroundNew-generation, cell-based assays have demonstrated a robust association of serum autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis, and brainstem encephalitis, as well as with neuromyelitis optica (NMO)-like or acute-disseminated encephalomyelitis (ADEM)-like presentations. However, only limited data are yet available on cerebrospinal fluid (CSF) findings in MOG-IgG-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD).ObjectiveTo describe systematically the CSF profile in children with MOG-EM.Material and methodsCytological and biochemical findings (including white cell counts [WCC] and differentiation; frequency and patterns of oligoclonal bands; IgG/IgM/IgA and albumin concentrations and CSF/serum ratios; intrathecal IgG/IgM/IgA fractions; locally produced IgG/IgM/IgA concentrations; immunoglobulin class patterns; IgG/IgA/IgM reibergrams; Link index; measles/rubella/zoster [MRZ] reaction; other anti-viral and anti-bacterial antibody indices; CSF total protein; CSF L-lactate) from 108 lumbar punctures in 80 pediatric patients of mainly Caucasian descent with MOG-EM were analyzed retrospectively.ResultsMost strikingly, CSF-restricted oligoclonal IgG bands, a hallmark of multiple sclerosis (MS), were absent in 89% of samples (N = 96), and the MRZ reaction, the most specific laboratory marker of MS known so far, in 100% (N = 29). If present at all, intrathecal IgG synthesis was low, often transient and mostly restricted to acute attacks. Intrathecal IgM synthesis was present in 21% and exclusively detectable during acute attacks. CSF WCC were elevated in 54% of samples (median 40 cells/μl; range 6-256; mostly lymphocytes and monocytes; > 100/μl in 11%). Neutrophils were present in 71% of samples; eosinophils, activated lymphocytes, and plasma cells were seen only rarely (all < 7%). Blood-CSF barrier dysfunction (as indicated by an elevated albumin CSF/serum ratio) was present in 46% of all samples (N = 79) and at least once in 48% of all patients (N = 67) tested. CSF alterations were significantly more frequent and/or more pronounced in patients with acute spinal cord or brain disease than in patients with acute ON and varied strongly depending on attack severity. CSF L-lactate levels correlated significantly with the spinal cord lesions load (measured in vertebral segments) in patients with acute myelitis (p = 0.0099). An analysis of pooled data from the pediatric and the adult cohort showed a significant relationship of QAlb (p < 0.0005), CST TP (p < 0.0001), and CSF L-lactate (p < 0.0003) during acute attacks with age.ConclusionMOG-IgG-associated EM in children is characterized by CSF features that are distinct from those in MS. With regard to most parameters, no marked differences between the pediatric cohort and the adult cohort analyzed in Part 1 were noted. Our findings are important for the differential diagnosis of pediatric MS and MOG-EM and add to the understanding of the immunopathogenesis of this newly described autoimmune disease.

Dataset Information

An association of Myelin Oligodendrocyte Glycoprotein (MOG) gene variants with white matter volume in pediatric obsessive-compulsive disorder.

Publications

An association of Myelin Oligodendrocyte Glycoprotein (MOG) gene variants with white matter volume in pediatric obsessive-compulsive disorder.

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