PMC:5590178 / 3959-5726 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/5590178","sourcedb":"PMC","sourceid":"5590178","source_url":"https://www.ncbi.nlm.nih.gov/pmc/5590178","text":"Although AxD can be diagnosed based on comprehensive evaluation of patient history, physical examination, brain MRI, GFAP sequencing and cerebral biopsy, GFAP sequencing and cerebral biopsy remain to be the best diagnostic approaches [3, 10]. Detection of Rosenthal fibers through cerebral biopsy is considered to be one of the best diagnostic approaches. However, most putative AxD patients with GFAP mutations did not undergo cerebral biopsy [12–14] as it is an invasive procedure. In addition, Rosenthal fibers are not a pathognomonic feature of AxD because they are also occasionally found in astrocytic tumors, ependymoma, hamartomas, craniopharyngioma, pineal cysts, glial scars and multiple sclerosis [3, 15]. Hence, DNA sequencing is the only definitive diagnostic approach for AxD under most circumstances. However, identification of GFAP mutations in putative AxD patients does not guarantee that these mutations are associated with AxD because it is feasible that these mutations are just variants of unknown significance. Therefore, it is imperative to determine whether the GFAP mutations found in tentative AxD patients are disease-causing. To this end, two methods have been employed. First, an in vitro assembly assay was performed with recombinant mutant GFAPs purified from E. coli and the formation of aggregates was then assessed. Second, an expression plasmid encoding the mutant GFAP was transfected into various mammalian cell lines, which were then observed for GFAP aggregates [13, 16–20]. However, these methods might not be suitable for testing the causality of the GFAP mutations, because both methods do not reflect the in vivo environment around astrocytes and the second method adopts a strong exogenous promoter to express mutant GFAP.","tracks":[{"project":"AxD_symptoms","denotations":[{"id":"T24","span":{"begin":256,"end":272},"obj":"Phenotype"},{"id":"T25","span":{"begin":497,"end":513},"obj":"Phenotype"},{"id":"T26","span":{"begin":616,"end":626},"obj":"Phenotype"},{"id":"T27","span":{"begin":628,"end":638},"obj":"Phenotype"},{"id":"T28","span":{"begin":640,"end":657},"obj":"Phenotype"},{"id":"T29","span":{"begin":659,"end":671},"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_0100320"},{"id":"A26","pred":"hp_id","subj":"T26","obj":"http://purl.obolibrary.org/obo/HP_0002888"},{"id":"A27","pred":"hp_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/HP_0010566"},{"id":"A28","pred":"hp_id","subj":"T28","obj":"http://purl.obolibrary.org/obo/HP_0030062"},{"id":"A29","pred":"hp_id","subj":"T29","obj":"http://purl.obolibrary.org/obo/HP_0012683"},{"subj":"T24","pred":"source","obj":"AxD_symptoms"},{"subj":"T25","pred":"source","obj":"AxD_symptoms"},{"subj":"T26","pred":"source","obj":"AxD_symptoms"},{"subj":"T27","pred":"source","obj":"AxD_symptoms"},{"subj":"T28","pred":"source","obj":"AxD_symptoms"},{"subj":"T29","pred":"source","obj":"AxD_symptoms"}]},{"project":"2_test","denotations":[{"id":"28882119-14572141-12765623","span":{"begin":235,"end":236},"obj":"14572141"},{"id":"28882119-14770299-12765624","span":{"begin":238,"end":240},"obj":"14770299"},{"id":"28882119-18004641-12765625","span":{"begin":445,"end":447},"obj":"18004641"},{"id":"28882119-15732097-12765625","span":{"begin":445,"end":447},"obj":"15732097"},{"id":"28882119-21165639-12765625","span":{"begin":445,"end":447},"obj":"21165639"},{"id":"28882119-14572141-12765626","span":{"begin":709,"end":710},"obj":"14572141"},{"id":"28882119-16687524-12765627","span":{"begin":712,"end":714},"obj":"16687524"},{"id":"28882119-15732097-12765628","span":{"begin":1503,"end":1505},"obj":"15732097"},{"id":"28882119-18197187-12765629","span":{"begin":1507,"end":1509},"obj":"18197187"},{"id":"28882119-27648269-12765629","span":{"begin":1507,"end":1509},"obj":"27648269"},{"id":"28882119-16826512-12765629","span":{"begin":1507,"end":1509},"obj":"16826512"},{"id":"28882119-8810256-12765629","span":{"begin":1507,"end":1509},"obj":"8810256"},{"id":"28882119-24755947-12765629","span":{"begin":1507,"end":1509},"obj":"24755947"}],"attributes":[{"subj":"28882119-14572141-12765623","pred":"source","obj":"2_test"},{"subj":"28882119-14770299-12765624","pred":"source","obj":"2_test"},{"subj":"28882119-18004641-12765625","pred":"source","obj":"2_test"},{"subj":"28882119-15732097-12765625","pred":"source","obj":"2_test"},{"subj":"28882119-21165639-12765625","pred":"source","obj":"2_test"},{"subj":"28882119-14572141-12765626","pred":"source","obj":"2_test"},{"subj":"28882119-16687524-12765627","pred":"source","obj":"2_test"},{"subj":"28882119-15732097-12765628","pred":"source","obj":"2_test"},{"subj":"28882119-18197187-12765629","pred":"source","obj":"2_test"},{"subj":"28882119-27648269-12765629","pred":"source","obj":"2_test"},{"subj":"28882119-16826512-12765629","pred":"source","obj":"2_test"},{"subj":"28882119-8810256-12765629","pred":"source","obj":"2_test"},{"subj":"28882119-24755947-12765629","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"AxD_symptoms","color":"#ecc693","default":true},{"id":"2_test","color":"#ac93ec"}]}]}}