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

Abstract

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

Cases: 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.

Conclusions: 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.