Clinical, Neuropathological, and Genetic Characteristics of the Novel IVS9+1delG GRN Mutation in a Patient with Frontotemporal Dementia

Article type: Research Article

Authors: Taipa, Ricardo^{a; *} | Tuna, Assunção^b | Damásio, Joana^b | Pinto, Pedro S.^c | Cavaco, Sara^d | Pereira, Sonia^e | Milterberger-Miltenyi, Gabriel^e | Galimberti, Daniela^f | Melo-Pires, Manuel^a

Affiliations: [a] Neuropathology Unit, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal | [b] Department of Neurology, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal | [c] Department of Neuroradiology, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal | [d] Neuropsychology Unit, Hospital Santo António, Centro Hospitalar do Porto, Porto, Portugal | [e] Instituto de Medicina Molecular, Faculdade Medicina, Universidade de Lisboa, Lisboa, Portugal | [f] Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy

Correspondence: [*] Correspondence to: Ricardo Taipa, MD, Neuropathology Unit, Hospital de Santo António, Centro Hospitalar do Porto, Largo Prof. Abel Salazar – 4099-001, Porto, Portugal. Tel: +351 915 677 563; Fax: +351 222 002 479; Emails: rtaipa.neuropat@chporto.min-saude.pt; ricardotaipa@gmail.com.

Abstract: Frontotemporal lobar degeneration (FTLD) refers to a clinically, pathologically, and genetically heterogeneous group of dementias that arises from the degeneration of the frontal and temporal lobes. Mutations in the progranulin gene (GRN) are a major cause of FTLD with TDP-43 inclusions. Herein, we describe the clinical, neuropathological, and genetic findings in a case of autosomal dominant behavioral variant of frontotemporal dementia (bvFTD) with asymmetrical parkinsonism and prominent visuospatial deficits that carries a novel GRN mutation. This case highlights important clinical characteristics that seem to be common in FTLD GRN-associated patients, such as asymmetrical parkinsonism and parietal symptoms, and that are correlated to the pathological involvement of striatum (rather than substantia nigra in our case) and parietal lobe. We also emphasize that plasma progranulin level can be useful to infer about the pathogenicity of new GRN mutations.

Keywords: Frontotemporal lobar degeneration (FTLD), parkinsonism, parietal lobe, progranulin, TDP43

DOI: 10.3233/JAD-2012-112084

Journal: Journal of Alzheimer's Disease, vol. 30, no. 1, pp. 83-90, 2012