Article: article from journal or magazin.
Case report (case report): feedback on an observation with a short commentary.
Progranulin gene mutation with an unusual clinical and neuropathologic presentation.
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
Progranulin gene (PGRN) mutations cause frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Patients usually present with a frontotemporal dementia syndrome and have prominent atrophy and neuronal loss in frontal and temporal cortices and the striatum, with neuronal intranuclear and cytoplasmic inclusions. Clinical, neuropathological, and genetic studies are reported on an individual with PGRN mutation and her family members. We describe a patient with a PGRN c.26C>A mutation who presented with progressive stuttering dysarthria, oculomotor abnormalities, choreic buccolingual movements, and mild parkinsonism. Two other family members were affected, one with a behavioral variant frontotemporal dementia syndrome, the other with a diagnosis of probable Alzheimer's disease. At autopsy there was no neuronal loss in the cortex or medial temporal lobe structures, but there was striatal gliosis. Immunohistochemistry for ubiquitin and TDP-43 revealed neuronal cytoplasmic and intranuclear inclusions as well as neurites. This study further expands the clinical and pathological spectrum of PGRN mutations, and suggests the diagnosis could be missed in some individuals with atypical presentations.
Atrophy, Chromosome Aberrations, DNA Mutational Analysis, Dementia/genetics, Dementia/pathology, Diagnosis, Differential, Dominance, Cerebral/physiology, Dysarthria/genetics, Dysarthria/pathology, Female, Frontal Lobe/pathology, Genes, Dominant/genetics, Humans, Inclusion Bodies/pathology, Intercellular Signaling Peptides and Proteins/genetics, Intranuclear Inclusion Bodies/pathology, Middle Aged, Movement Disorders/genetics, Movement Disorders/pathology, Neurites/pathology, Neurologic Examination, Neurons/pathology, Oculomotor Nerve Diseases/genetics, Oculomotor Nerve Diseases/pathology, Parkinsonian Disorders/genetics, Parkinsonian Disorders/pathology, Pedigree, Putamen/pathology, Stuttering/genetics, Stuttering/pathology, Temporal Lobe/pathology, Ubiquitin/analysis
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