{Reference Type}: Case Reports
{Title}: A novel GRN mutation in an Italian patient with non-fluent variant of primary progressive aphasia at onset: a longitudinal case report.
{Author}: Castelnovo V;Canu E;Domi T;Pozzi L;Vignaroli F;Spinelli EG;Ghirelli A;Tondo G;Comi C;Riva N;Quattrini A;Carrera P;Filippi M;Agosta F;
{Journal}: Front Neurosci
{Volume}: 17
{Issue}: 0
{Year}: 2023
{Factor}: 5.152
{DOI}: 10.3389/fnins.2023.1204504
{Abstract}: UNASSIGNED: We report the clinical presentation and evolution of a case with a novel Progranulin gene (GRN) mutation and non-fluent language disturbances at onset.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.