Juvenile frontotemporal dementia with parkinsonism associated with tau mutation G389R.
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.
Department of Neurology, Maison Blanche Hospital, Reims University Hospital, Reims, France.
Marie-Pierre
MP
Chaunu
Vincent
V
Deramecourt
Valérie
V
Buée-Scherrer
Isabelle
I
Le Ber
Alexis
A
Brice
Nathalie
N
Ehrle
Khalid
K
El Hachimi
Michel
M
Pluot
Claude-Alain
CA
Maurage
Serge
S
Bakchine
Luc
L
Buée
D000293:Adolescent; D000367:Age Factors; D003062:Codon / Q000235:genetics; D042241:Early Diagnosis; D017809:Fatal Outcome; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D016875:tau Proteins / Q000235:genetics*
D003062:Codon; C054369:MAPT protein, human; D016875:tau Proteins
Early onset dementia; G389R mutation; MAPT; Pick bodies; frontotemporal lobar degeneration; tau protein