PMC:4766795 / 3328-5409 JSONTXT

{"project":"AxD_symptoms","denotations":[{"id":"T24","span":{"begin":214,"end":230},"obj":"Phenotype"},{"id":"T25","span":{"begin":388,"end":395},"obj":"Phenotype"},{"id":"T26","span":{"begin":602,"end":618},"obj":"Phenotype"},{"id":"T27","span":{"begin":628,"end":641},"obj":"Phenotype"},{"id":"T28","span":{"begin":873,"end":889},"obj":"Phenotype"},{"id":"T29","span":{"begin":894,"end":907},"obj":"Phenotype"},{"id":"T30","span":{"begin":932,"end":949},"obj":"Phenotype"}],"attributes":[{"id":"A24","pred":"hp_id","subj":"T24","obj":"http://purl.obolibrary.org/obo/HP_0100320"},{"id":"A25","pred":"hp_id","subj":"T25","obj":"http://purl.obolibrary.org/obo/HP_0002171"},{"id":"A26","pred":"hp_id","subj":"T26","obj":"http://purl.obolibrary.org/obo/HP_0100320"},{"id":"A27","pred":"hp_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/HP_0011096"},{"id":"A28","pred":"hp_id","subj":"T28","obj":"http://purl.obolibrary.org/obo/HP_0100320"},{"id":"A29","pred":"hp_id","subj":"T29","obj":"http://purl.obolibrary.org/obo/HP_0011096"},{"id":"A30","pred":"hp_id","subj":"T30","obj":"http://purl.obolibrary.org/obo/HP_0003651"}],"text":"Postmortem examination of the cerebrum, cerebellum, and brainstem showed mild-to-moderate atrophy with foci of grayish discolorations noted in the white matter. Histopathologic examination revealed accumulation of Rosenthal fibers, in a scattered and perivascular arrangement in regions adjacent to the lateral ventricle (Figure 1C), cerebellum, and left hippocampus. Background reactive gliosis as well as white matter rarefaction (Figure 1D, Figure 1E) was present. Depopulation of neurons was noted in the dentate nucleus of the cerebellum. The pons was remarkable for periventricular and scattered Rosenthal fibers. Foci of demyelination in the parietal lobe, cerebellar white matters, and corpus callosum were confirmed with Luxol fast blue staining (Figure 1F, Figure 1G, Figure 1H). Examination of the medulla, including the tegmentum, demonstrated large numbers of Rosenthal fibers and demyelination (Figure 2A, Figure 2B); foamy macrophages with intracellular LFB-positive myelin were also identified (Figure 2C). Relative preservation of axons were observed with a neurofilament protein immunostain (Figure 2D). Immunostains for ubiquitin, α-synuclein and τ-proteins showed no glial intracytoplasmic inclusions typically seen in disorders such as multiple system atrophy (MSA) or immunopositivity for neuronal τ-protein or ballooned neurons in the neocortices as seen in corticobasal ganglionic degeneration (CBD). Molecular testing revealed a missense mutation in the GFAP gene involving nucleotide position 383 of codon 128, resulting in an amino acid change from aspartic acid (D) to asparagine (N)(i.e., GFAP c.382 G\u003eA 9p.Asp128Asn) (dbSNP Reference: rs267607509). In silico analysis using polymorphism phenotyping tool (PolyPhen-2.2.2) revealed that this sequence alteration is “probably damaging”. To date, this specific mutation has only been noted in two other cases of AxD [6, 7]; however, these two cases most likely represent the same patient, as both are presented by the same authors/institution and highlight patients with the same age and disease duration."}

{"project":"2_test","denotations":[{"id":"25997626-18684770-22409919","span":{"begin":1893,"end":1894},"obj":"18684770"},{"id":"25997626-18388212-22409920","span":{"begin":1896,"end":1897},"obj":"18388212"}],"text":"Postmortem examination of the cerebrum, cerebellum, and brainstem showed mild-to-moderate atrophy with foci of grayish discolorations noted in the white matter. Histopathologic examination revealed accumulation of Rosenthal fibers, in a scattered and perivascular arrangement in regions adjacent to the lateral ventricle (Figure 1C), cerebellum, and left hippocampus. Background reactive gliosis as well as white matter rarefaction (Figure 1D, Figure 1E) was present. Depopulation of neurons was noted in the dentate nucleus of the cerebellum. The pons was remarkable for periventricular and scattered Rosenthal fibers. Foci of demyelination in the parietal lobe, cerebellar white matters, and corpus callosum were confirmed with Luxol fast blue staining (Figure 1F, Figure 1G, Figure 1H). Examination of the medulla, including the tegmentum, demonstrated large numbers of Rosenthal fibers and demyelination (Figure 2A, Figure 2B); foamy macrophages with intracellular LFB-positive myelin were also identified (Figure 2C). Relative preservation of axons were observed with a neurofilament protein immunostain (Figure 2D). Immunostains for ubiquitin, α-synuclein and τ-proteins showed no glial intracytoplasmic inclusions typically seen in disorders such as multiple system atrophy (MSA) or immunopositivity for neuronal τ-protein or ballooned neurons in the neocortices as seen in corticobasal ganglionic degeneration (CBD). Molecular testing revealed a missense mutation in the GFAP gene involving nucleotide position 383 of codon 128, resulting in an amino acid change from aspartic acid (D) to asparagine (N)(i.e., GFAP c.382 G\u003eA 9p.Asp128Asn) (dbSNP Reference: rs267607509). In silico analysis using polymorphism phenotyping tool (PolyPhen-2.2.2) revealed that this sequence alteration is “probably damaging”. To date, this specific mutation has only been noted in two other cases of AxD [6, 7]; however, these two cases most likely represent the same patient, as both are presented by the same authors/institution and highlight patients with the same age and disease duration."}