Progranulin Mutation Manifesting as Parkinson Disease: A Case Series from the PADUA-CESNE Cohort

Mutations in progranulin (GRN) are associated with frontotemporal dementia, although a Parkinson disease (PD) phenotype is uncommon, especially in young patients.

We report three subjects from the PADUA-CESNE cohort, meeting diagnostic criteria for PD, with onset under age 55. All had good response to dopaminergic therapy, abnormal dopamine transporter single-photon emission computed tomography striatal uptake and a disease course consistent with PD, without clear atypical features, behavioral, or cognitive deficits. Genetic testing (next-generation sequencing [NGS] panel) revealed three different variants in GRN gene. Skin biopsy immunohistochemistry analysis showed phosphorylated α-synuclein deposition in two and was negative in one subject.

Our findings expand the phenotypic spectrum of GRN mutations, showing that patients can present with clinical manifestations of PD, including phosphorylated synuclein pathology in the skin, with a relatively young age of onset. Our observations support the use of broad-spectrum NGS panels to properly guide patients in counseling and accurately allocate them to disease-modifying therapies.