Juvenile Frontotemporal Dementia with Parkinsonism Associated with Tau Mutation G389R

Article type: Research Article

Authors: Chaunu, Marie-Pierre^{a; 1} | Deramecourt, Vincent^{b; c; d; 1} | Buée-Scherrer, Valérie^d | Le Ber, Isabelle^{e; f} | Brice, Alexis^{e; f} | Ehrle, Nathalie^a | El Hachimi, Khalid^{f; g} | Pluot, Michel^h | Maurage, Claude-Alain^{c; d} | Bakchine, Serge^{a; *} | Buée, Luc^{d; *}

Affiliations: [a] Department of Neurology, Maison Blanche Hospital, Reims University Hospital, Reims, France | [b] Univ Lille Nord de France, Lille University Hospital, Lille, France | [c] Univ Lille Nord de France, Histology and Neuropathology Departments, Lille University Hospital, Lille, France | [d] INSERM U837 and Univ Lille Nord de France, Jean-Pierre Aubert Research Centre, Lille, France | [e] Department of Genetics and Cytogenetics, AP-HP, Pitié-Salpêtrière Hospital, Paris, France | [f] CR-ICM UMRS975, Paris, France | [g] Ecole Pratique des Hautes Etudes, Paris, France | [h] Department of Pathology, Robert Debré Hospital, Reims University Hospital, Reims, France

Correspondence: [*] Correspondence to: Serge Bakchine, Service de Neurologie, Hôpital Maison blanche, Centre hospitalier et Universitaire, 51100, Reims, France. Tel.: +33 326 78 71 35; Fax: +33 326 78 43 19; E-mail: sbakchine@chu-reims.fr; Luc Buée, INSERM U837, place de Verdun, 59045 Lille, France. Tel.: +33 320 29 88 66; Fax: +33 320 53 85 62; E-mail: luc.buee@inserm.fr.

Note: [1] These authors contributed equally to this article.

Abstract: Frontotemporal lobe degeneration includes a large spectrum of neurodegenerative disorders. Patients with frontotemporal dementia with parkinsonism linked to chromosome 17 exhibit heterogeneity in both clinical and neuropathological features. Here, we report the case of a young patient with a G389R mutation. This teenager girl was 17 years old when she progressively developed severe behavioral disturbances. First, she was considered to be suffering from atypical depression. After 2 years, she was referred to the department of neurology. By this time, the patient exhibited typical frontotemporal dementia with mild extrapyramidal disorders. The main behavioral features included apathy and reduced speech output. MRI and SPECT showed a frontotemporal atrophy and hypofixation, respectively. She died 7 years after onset. Three relatives on her father side had also died after early onset dementia. Genetic testing revealed a heterozygous guanine to cytosine mutation at the first base of codon 389 (Exon 13) of MAPT, the tau gene, resulting in a glycine to arginine substitution, in the patient and her non-affected father. Postmortem neuropathological and biochemical data indicate a Pick-like tau pathology but with phosphoserine 262-positive immunoreactivity. This case is remarkable because of the extremely early onset of the disease.

Keywords: Early onset dementia, frontotemporal lobar degeneration, G389R mutation, MAPT, Pick bodies, tau protein

DOI: 10.3233/JAD-130413

Journal: Journal of Alzheimer's Disease, vol. 37, no. 4, pp. 769-776, 2013