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Adult-onset Alexander disease with a heterozygous D128N GFAP mutation: a pathological study

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dc.contributor.authorCabrera Galván, Juan José
dc.contributor.authorMartínez Martin, María Soledad
dc.contributor.authorDéniz García, Daniel
dc.contributor.authorAraujo Ruano, Eduardo
dc.contributor.authorTravieso Aja, María del Mar
dc.date.accessioned2022-07-11T08:03:55Z
dc.date.available2022-07-11T08:03:55Z
dc.date.issued2019
dc.description.abstractThe various forms of Alexander disease (AD) have been linked to heterozygous point mutations in the coding region of the Human glial fibrillary acidic protein (GFAP) gene. The aim of this study was to confirm and characterise an adult variant of AD based on the presence of Rosenthal fibres, which were identified at brain autopsy. We performed histological and immunohistochemical studies and mutation screening by cycle sequencing of exons 1, 4, 6, and 8. A heterozygous D128N GFAP mutation, previously described in three other cases of adult-onset AD (AOAD), was genetically confirmed. The mutation was seemingly sporadic. Symptoms of the female, 65-year-old patient started with occasionally asymmetric motor impairment and concluded, 23 months later, with a lack of spontaneous movement in all four limbs, reduced consciousness, an acute respiratory problem, and eventually lethal exitus. The most striking characteristics were a cerebellar syndrome with subsequent clinical signs due to brainstem and spinal cord involvement. The final diagnosis was based on a complete autopsy, detection of Rosenthal fibres, GFAP, vimentin, alpha B-crystallin, ubiquitin, hsp27, neurofilament, and synaptophysin, and the identification of the corresponding GFAP gene mutation. Blood analyses were positive for ANA and rheumatoid factor. In conclusion, this work describes sporadic, rapidly advancing AOAD in a female patient and links it with other published cases with the same mutation. Reflections are provided on the influence of vasculitis and ANA in AD as well as the presence of Rosenthal fibres in the neurohypophysis.es
dc.formatapplication/pdfes
dc.format.extent16es
dc.identifier.doihttps://doi.org/10.14670/HH-18-110
dc.identifier.eisbnHistology and Histopathology, Vol.34, nº9, (2019)es
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/122269
dc.languageenges
dc.publisherUniversidad de Murcia. Departamento de Biología Celular e Histologíaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAlexander diseasees
dc.subjectD128N GFAP mutationes
dc.subjectImmunohistochemistryes
dc.subjectMRIes
dc.subjectPathologyes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleAdult-onset Alexander disease with a heterozygous D128N GFAP mutation: a pathological studyes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.34, nº9 (2019)