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A novel GRN mutation in an Italian patient with non-fluent variant of primary progressive aphasia at onset: a longitudinal case report

OBJECTIVES: We report the clinical presentation and evolution of a case with a novel Progranulin gene (GRN) mutation and non-fluent language disturbances at onset. MATERIALS AND METHODS: A 60 year-old, white patient was followed due to a history of language disturbances. Eighteen months after onset,...

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Detalles Bibliográficos
Autores principales: Castelnovo, Veronica, Canu, Elisa, Domi, Teuta, Pozzi, Laura, Vignaroli, Francesca, Spinelli, Edoardo Gioele, Ghirelli, Alma, Tondo, Giacomo, Comi, Cristoforo, Riva, Nilo, Quattrini, Angelo, Carrera, Paola, Filippi, Massimo, Agosta, Federica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296183/
https://www.ncbi.nlm.nih.gov/pubmed/37383099
http://dx.doi.org/10.3389/fnins.2023.1204504
Descripción
Sumario:OBJECTIVES: We report the clinical presentation and evolution of a case with a novel Progranulin gene (GRN) mutation and non-fluent language disturbances at onset. MATERIALS AND METHODS: A 60 year-old, white patient was followed due to a history of language disturbances. Eighteen months after onset, the patient underwent FDG positron emission tomography (PET), and at month 24 was hospitalized to perform neuropsychological evaluation, brain 3 T MRI, lumbar puncture for cerebrospinal fluid (CSF) analysis, and genotyping. At month 31, the patient repeated the neuropsychological evaluation and brain MRI. RESULTS: At onset the patient complained prominent language production difficulties, such as effortful speech and anomia. At month 18, FDG-PET showed left fronto-temporal and striatal hypometabolism. At month 24, the neuropsychological evaluation reported prevalent speech and comprehension deficits. Brain MRI reported left fronto-opercular and striatal atrophy, and left frontal periventricular white matter hyperintensities (WMHs). Increased CSF total tau level was observed. Genotyping revealed a new GRN c.1018delC (p.H340TfsX21) mutation. The patient received a diagnosis of non-fluent variant of primary progressive aphasia (nfvPPA). At month 31, language deficits worsened, together with attention and executive functions. The patient presented also with behavioral disturbances, and a progressive atrophy in the left frontal-opercular and temporo-mesial region. DISCUSSION AND CONCLUSION: The new GRN p.H340TfsX21 mutation resulted in a case of nfvPPA characterized by fronto-temporal and striatal alterations, typical frontal asymmetric WMHs, and a fast progression toward a widespread cognitive and behavioral impairment, which reflects a frontotemporal lobar degeneration. Our findings extend the current knowledge of the phenotypic heterogeneity among GRN mutation carriers.