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Subject | Predicate | Object |
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http://purl.uniprot.org/citations/24589341 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/24589341 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/24589341 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundIdentifying genetic syndromes that lead to significant atopic disease can open new pathways for investigation and intervention in allergy.ObjectiveWe sought to define a genetic syndrome of severe atopy, increased serum IgE levels, immune deficiency, autoimmunity, and motor and neurocognitive impairment.MethodsEight patients from 2 families with similar syndromic features were studied. Thorough clinical evaluations, including brain magnetic resonance imaging and sensory evoked potentials, were performed. Peripheral lymphocyte flow cytometry, antibody responses, and T-cell cytokine production were measured. Whole-exome sequencing was performed to identify disease-causing mutations. Immunoblotting, quantitative RT-PCR, enzymatic assays, nucleotide sugar, and sugar phosphate analyses, along with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry of glycans, were used to determine the molecular consequences of the mutations.ResultsMarked atopy and autoimmunity were associated with increased T(H)2 and T(H)17 cytokine production by CD4(+) T cells. Bacterial and viral infection susceptibility were noted along with T-cell lymphopenia, particularly of CD8(+) T cells, and reduced memory B-cell numbers. Apparent brain hypomyelination resulted in markedly delayed evoked potentials and likely contributed to neurologic abnormalities. Disease segregated with novel autosomal recessive mutations in a single gene, phosphoglucomutase 3 (PGM3). Although PGM3 protein expression was variably diminished, impaired function was demonstrated by decreased enzyme activity and reduced uridine diphosphate-N-acetyl-D-glucosamine, along with decreased O- and N-linked protein glycosylation in patients' cells. These results define a new congenital disorder of glycosylation.ConclusionsAutosomal recessive hypomorphic PGM3 mutations underlie a disorder of severe atopy, immune deficiency, autoimmunity, intellectual disability, and hypomyelination."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jaci.2014.02.013"xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jaci.2014.02.013"xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Ichikawa M."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Ichikawa M."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Jing H."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Jing H."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Yu X."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Yu X."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Datta S."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Datta S."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Freeze H.H."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Freeze H.H."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Kim E.S."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Kim E.S."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Holland S.M."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Holland S.M."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Milner J.D."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Milner J.D."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Wolfe L.A."xsd:string |
http://purl.uniprot.org/citations/24589341 | http://purl.uniprot.org/core/author | "Wolfe L.A."xsd:string |