Affiliations: [a] Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| [b] Department of Psychiatry and Behavioral Sciences, University of Washington, WA, USA
Correspondence:
[*]
Correspondence to: Shifu Xiao, Shanghai Mental HealthCenter, Shanghai Jiao Tong University School of Medicine, No. 600 South Wanping Road, Xuhui Distinct, Shanghai, China. Tel.: +86 021 64387250; E-mail: [email protected].
Abstract: Frontotemporal dementia includes a large spectrum of neurodegenerative disorders. Here, we report the case of a young patient with MAPT mutation G389R, who was 27 years old when he progressively developed severe behavioral disturbances. Initially, he presented with slowly progressive personality change. After 1 year, he exhibited moderate dementia with extrapyramidal and pyramidal symptoms. MRI showed frontotemporal atrophy. He rapidly progressed to severe dementia 3 years after onset. Genetic testing revealed a heterozygous guanine to cytosine mutation at the first base of codon 389 (c.1165G>A) of MAPT, the tau gene, resulting in a glycine to arginine substitution in the patient and two unaffected relatives. We predicted the model of mutant tau protein through I-TASSER software, and speculated the structural change of tau protein caused by mutant site. We also detected the MAPT gene transcript and methylation of samples from peripheral blood leucocytes in an attempt to explain the possible mechanisms of incomplete penetrance, although there were not positive findings. This case is remarkable because of the early onset and rapid progression of the disease.
Keywords: Early onset dementia, frontotemporal dementia, G389R mutation, MAPT, protein structure predicting
