PMC:3654953 / 22982-24491
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3654953","sourcedb":"PMC","sourceid":"3654953","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3654953","text":"A substantial fraction of AOAD patients are sporadic, the most frequent symptoms being related to bulbar dysfunction, pyramidal involvement and cerebellar ataxia. Palatal myoclonus is frequent in, and highly suggestive of, AOAD [4]. Other findings include cognitive deterioration, sleep disorders, and dysautonomia. The course is slowly progressive and fluctuations may occur. Ultimately, the diagnosis is strongly suggested by a typical MRI pattern, and confirmed by GFAP gene analysis. In our family, Pt1 has been suffering of slowly progressive cognitive impairment and mild movement disorder, whereas her younger half-brother (Pt2) has severe MND. In spite of clinical diversity, the cardinal MRI features of AOAD [24] were present in both. The absence of mutation in the GFAP-α encoding gene prompted us to perform exome-NGS and eventually identify a unique mutation in alternative GFAP ex7A, not present in the healthy mother tested DNAs and with a deleterious outcome in a cellular model. These are in fact the first cases associated with a mutation in the GFAP-ϵ variant (GFAP-ϵR430H). Whilst this finding supports the idea that AOAD is almost invariably associated with abnormalities of GFAP, it also expands the spectrum of variants that should be included in the diagnostic screening. Due to the pedigree structure, the mutation has very likely been transmitted by maternal germinal mosaicism, since it was absent in other available family members, including the healthy mother of the two patients.","tracks":[{"project":"AxD_symptoms","denotations":[{"id":"T59","span":{"begin":144,"end":161},"obj":"Phenotype"},{"id":"T60","span":{"begin":163,"end":180},"obj":"Phenotype"},{"id":"T61","span":{"begin":302,"end":314},"obj":"Phenotype"},{"id":"T62","span":{"begin":548,"end":568},"obj":"Phenotype"},{"id":"T63","span":{"begin":578,"end":595},"obj":"Phenotype"}],"attributes":[{"id":"A59","pred":"hp_id","subj":"T59","obj":"http://purl.obolibrary.org/obo/HP_0001251"},{"id":"A60","pred":"hp_id","subj":"T60","obj":"http://purl.obolibrary.org/obo/HP_0010530"},{"id":"A61","pred":"hp_id","subj":"T61","obj":"http://purl.obolibrary.org/obo/HP_0012332"},{"id":"A62","pred":"hp_id","subj":"T62","obj":"http://purl.obolibrary.org/obo/HP_0100543"},{"id":"A63","pred":"hp_id","subj":"T63","obj":"http://purl.obolibrary.org/obo/HP_0100022"},{"subj":"T59","pred":"source","obj":"AxD_symptoms"},{"subj":"T60","pred":"source","obj":"AxD_symptoms"},{"subj":"T61","pred":"source","obj":"AxD_symptoms"},{"subj":"T62","pred":"source","obj":"AxD_symptoms"},{"subj":"T63","pred":"source","obj":"AxD_symptoms"}]},{"project":"2_test","denotations":[{"id":"23634874-18684770-81641091","span":{"begin":229,"end":230},"obj":"18684770"},{"id":"23634874-18388212-81641092","span":{"begin":719,"end":721},"obj":"18388212"},{"id":"T96897","span":{"begin":229,"end":230},"obj":"18684770"},{"id":"T44180","span":{"begin":719,"end":721},"obj":"18388212"}],"attributes":[{"subj":"23634874-18684770-81641091","pred":"source","obj":"2_test"},{"subj":"23634874-18388212-81641092","pred":"source","obj":"2_test"},{"subj":"T96897","pred":"source","obj":"2_test"},{"subj":"T44180","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"AxD_symptoms","color":"#93c5ec","default":true},{"id":"2_test","color":"#dfec93"}]}]}}