Rapidly Progressive Frontotemporal Dementia Associated with MAPT Mutation G389R

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.

额颞叶痴呆包含一大类神经退行性疾病。在此，我们报告一例携带微管相关蛋白tau（MAPT）基因G389R突变的年轻患者病例，他在27岁时逐渐出现严重的行为障碍。最初，他表现为缓慢进展的人格改变。1年后，他出现伴有锥体外系和锥体束症状的中度痴呆。磁共振成像（MRI）显示额颞叶萎缩。发病3年后，他迅速进展为重度痴呆。基因检测显示，tau基因MAPT的第389位密码子第一个碱基发生杂合的鸟嘌呤到胞嘧啶突变（c.1165G>A），导致患者以及两名未患病亲属的甘氨酸被精氨酸替代。我们通过I - TASSER软件预测了突变型tau蛋白的模型，并推测了突变位点导致的tau蛋白结构变化。我们还检测了外周血白细胞样本的MAPT基因转录本和甲基化情况，试图解释不完全外显的可能机制，尽管未得到阳性结果。该病例因疾病发病早且进展迅速而值得关注。